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Issue 41

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


Jennifer Desalvo MD; Alyssa Mancini MD; Hannah Smith MD 


  • Melatonin gummies – putting accurate labeling to bed. A recent study in JAMA analyzed the quantity of melatonin and cannabidiol (CBD) in 25 unique brands of over-the-counter melatonin gummies. One product did not contain any detectable levels of melatonin, and for those that did, the actual quantity of melatonin ranged from 74% to 347% of the labeled quantity.  Of five products with CBD as an ingredient, the actual quantity of CBD ranged from 104% to 118% of the labeled quantity.  Overall, 22 of 25 products (88%) were inaccurately labeled, with most products substantially exceeding the declared amount of melatonin and CBD.  For over-the-counter supplements, what you buy is not always what you get. (AM)

  • Personalized medicine may play a role in hypertension management, according to a recent double-blind, repeat crossover trial just published in JAMA. 270 Swedish adults with grade 1 hypertension underwent ambulatory blood pressure monitoring during treatment with each of four classes of anti-hypertensive medications (ACE inhibitor, ARB, thiazide, and calcium channel blocker) for nearly 2 months each, with repeat treatments for 2 randomly chosen classes.  Each treatment period, which lasted approximately 2 months, was separated by a washout.  There was significant individual variability in blood pressure response to different treatments, with estimates from mixed-effects modeling that personalizing anti-hypertensive regimens could add a further 4.4 mm Hg to systolic blood pressure decreases. (JD) 

  • Abdominal pain, diarrhea, rectal bleeding, and iron deficiency anemia–harbingers of early-onset colorectal cancer? According to a matched case-control study of >5000 US patients published in the Journal of the National Cancer Insitute, these four signs and symptoms were associated with an increased risk of early-onset (age <50 years) colorectal cancer (CRC).  Having 1, 2 or ≥3 of these signs and symptoms was associated with a 1.94, 3.59, and 6.52-fold increased risk of early-onset CRC, with significantly stronger associations with younger age (18-44 years old) and rectal cancer.  Only 50% of patients had symptoms starting < 3 months prior to diagnosis, with a longer diagnostic lag time of 8.7 months for those who experienced symptoms >3 months - 2 years before diagnosis. (JD) 

  • Bariatric Surgery for NASH–a new frontier. A recent multicenter, open-label trial, just published in Lancet, randomized nearly 300 adults with obesity (BMI 30-55 kg/m2) and histologically confirmed non-alcoholic steatohepatitis (NASH) to lifestyle and medication interventions, Roux-en-Y gastric bypass, or sleeve gastrectomy.  Patients who underwent bariatric surgery were 3.6 times more likely to experience histologic NASH resolution (without worsening fibrosis) by 1 year of follow-up compared to those receiving lifestyle and medication interventions  (56-57% versus 16%, p<0.0001). Clinicians should consider surgical referral in this population. (JD) 

  • Herbs to the rescue: XBJ for sepsis?  In EXIT-SEP, a double-blind, randomized, placebo-control trial just published in JAMA Internal Medicine, over 1800 ICU patients in China were randomized to a five day course of Xuebijing injection or saline placebo, in addition to standard sepsis management. Xuebijing (XBJ), an herbal intravenous preparation, was licensed in 2004 by the National Medical Products Administration in China for the treatment of sepsis and multiple organ dysfunction.  XBJ is thought to block endotoxin activity, downregulate inflammatory cytokines, and improve coagulopathy.  The 28-day mortality rate was lower in the XBJ group than in placebo (18.8% in XBJ vs 26.1% in placebo, p<0.001). There were no significant differences in adverse events between the two groups. (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.


Can artificial intelligence chatbot assistants improve communication between patients and clinicians?


A recent cross-sectional study published in JAMA Internal Medicine compared chatbot and physician responses to patient questions published in an online public social media forum (Reddit’s r/AskDocs).  Among 195 total questions and responses, evaluators preferred chatbot responses over physicians’ in >78% of evaluations, rating chatbot responses as higher quality and significantly more empathetic than physicians’ responses. The authors suggest that chatbots could assist clinicians and support staff in drafting responses to patient questions in the future, which may improve patient messaging quality and clinician productivity.  


– Jen Desalvo MD 


The Main Course

Alyssa Mancini MD 


The Main Course

Alyssa Mancini MD

Statins for Primary Prevention of Cardiovascular Disease in Patients with HIV…a REPRIEVE?

Advances in HIV treatment over the past few decades have greatly reduced AIDS-related complications and death.  Subsequently, cardiovascular disease (CVD) and other chronic conditions have become leading causes of morbidity and mortality in individuals with HIV, given a 1.5-2-fold increased risk of ischemic heart disease in this population.  Not only do those with HIV have an increased prevalence of traditional cardiovascular disease risk factors; there are also HIV-specific mechanisms such as immune activation and inflammation that contribute to higher CVD risk.  Furthermore, older antiretroviral regimens cause chronic metabolic derangements that have likely contributed as well.  Yet, despite these unique factors that increase cardiovascular risk, many of our commonly used atherosclerotic cardiovascular disease (ASCVD) risk calculators do not take into account HIV status or other inflammatory disease states.  

To address questions about CVD risk stratification and reduction in this population, the National Institutes of Health (NIH) started the Randomized Trial to Prevent Vascular Events in HIV (a.k.a. REPRIEVE), the first large-scale clinical study to test a primary cardiovascular prevention strategy in people living with HIV.  Now the trial has now been stopped early, as described in the April 11th NIH press release, after a planned interim analysis found adequate evidence of efficacy in CVD risk reduction with pitavastatin over placebo. 

Breaking it Down

From 2015 to 2019, REPRIEVE enrolled 7,769 participants with HIV at over 100 clinical sites across 12 countries and 5 continents (mean age 50 years, 32% women, >40% Black or African American, mean of 13 years living with HIV).  Participants, aged 40 - 75, were all taking antiretroviral therapy, all had CD4+ cell counts greater than 100 cells/mm3 of blood at enrollment, and all had low-to-moderate traditional cardiovascular disease risk that would not typically be an indication for statin treatment (according to the 2013 ACC/AHA guidelines). Exclusion criteria included prior history of ASCVD, diabetes if LDL > 70 mg/dL, and the use of a statin, gemfibrozil, or PCSK9-inhibitor in the past 90 days, among others.  Participants were randomly assigned to receive 4 mg of pitavastatin (which is safe to use with all prescribed antiretroviral therapy regimens) daily or placebo. There were scheduled visits approximately every 4 months, and average trial participation was about 6 years. The primary outcome was time to the first event of a composite of major cardiovascular events, including atherosclerotic or other cardiovascular death, nonfatal MI, unstable angina hospitalization, coronary or peripheral arterial revascularization, nonfatal stroke/TIA, and urgent peripheral arterial disease ischemic event.  Secondary outcomes included time to the first of each individual component of the primary endpoint, all-cause mortality, all-cause mortality and/or MACE, fasting LDL and HDL cholesterol levels, and adverse events, among others.

The planned interim analysis found that participants who took pitavastatin had a 35% lower risk of composite major cardiovascular event, compared to those receiving placebo.  Adverse drug events observed in the study were similar to those for the general population taking statin therapy.


The Takeaways

Interim analysis of REPRIEVE has shown that a daily statin medication reduces the risk of major cardiovascular events in individuals living with HIV who otherwise would not be prescribed a statin according to the latest 2019 ACC/AHA guidelines.  From what we can tell so far, these results seem generalizable to the population with HIV, the intervention seems fairly safe, and the outcomes are clinically important. We still don’t know if there are specific subpopulations that derive more benefit than others, but these data were compelling enough that the Data Safety and Monitoring Board (DSMB) recommended stopping the trial early because of the adequate evidence of efficacy for pitavastatin compared to placebo in this population.  Given that these results could be quite practice-changing for a large population, we eagerly await the formally published results, coming soon. 


Read the Interim Trial Announcement HERE 




Before you go....
we’ve got a few nibbles!
  • Consolidate your learning with a Quiz!  

This week on Curbsiders: We’ve got an ACP Recap bonanza. Get all the clinical pearls you might have missed in San Diego–whether you were at ACP or not–in Episode #394. We’ve got a wide-ranging set of facts, covering hypogonadism, air rage, GU symptoms in menopause, and pickle juice for leg cramps in cirrhosis (yes, we covered this already, but it’s such a crowd favorite…). 

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Until next time, keep that brain hole digesting! 

The Curbsiders Digest
Issue 41

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


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

Kate Grant reports no disclosures 


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