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Jun 7, 2019

Option chain

The story

Big data is a big deal in premenopausal hormone receptor positive (HR+) breast cancer. Large trials – fresh from ASCO – add evermore complexity to the field.  

Far out

Progression-free survival is nice, but overall survival (OS) is still the queen of clinical trial metrics. Ribociclib became the first of the CDK4/6 inhibitor class of medications to demonstrate a significant OS benefit in the 670-patient MONALEESA-7 trial. Enrolled patients were pre- or perimenopausal – a higher risk group than postmenopausal patients – with hormone receptor HR+/HER2- advanced breast cancer. The addition of ribociclib to endocrine therapy in the first-line setting led to an estimated 70% OS at 42 months compared to 46% for endocrine therapy plus placebo. No new safety signals were seen. 
NEJM

Game of inches

Old school clinical risk still holds weight. A subgroup analysis that dug deep into the data from last year's 9,400 patient TAILORx trial, which validated use of a 21-gene expression assay to guide decisions on adjuvant chemotherapy in HR+/HER2- early stage breast cancer, found that tumor size and histologic grade helped inform risk of distant recurrence for young women with intermediate gene-based recurrence scores. The results suggest that further endocrine or chemotherapy could be of benefit in these women, though with no conclusive proof, they also demonstrate how complex it can be to apply data from large trials to individual patients.
NEJM

Say it on rounds

When you'll walk anywhere, as long as it's the opposite direction of rounds

A little goes a long way. While 10,000 steps is a lofty goal, there's not much scientific backing behind the number. A prospective cohort of 16,700 older women (mostly age > 70) asked participants to wear a step-counter for 7 days and then tracked long-term results. More steps were better: those in the lowest quartile (median 2,700 per steps per day) saw increased mortality compared to all other groups over 4-year follow-up, including those in the next lowest quartile (median of 4,700 steps per day). Mean steps per day was 5,500. 
JAMA Intern Med

When tech support has you on indefinite hold

Better than a doctor's office. Researchers conducted an audit study to check for appointment availability and time to buprenorphine initation in 6 US states with a high burden of opiate use disorder. All callers (researchers posing as patients) reported current heroin use. Roughly 40% of callers were denied a clinic appointment with a buprenorphine prescriber, and most were not offered the opportunity for buprenorphine induction at first visit. For clinicians who were accepting new patients, wait times for new visits were often less than 1 - 2 weeks, highlighting scarcity of prescribers as a key barrier to care.  
Annals

When none of your AM labs were drawn

Placing an order isn't always enough. Teens account for nearly half of all sexually transmitted infections (STIs), but a retrospective cohort involving adolescents seeking care at 2 pediatric EDs in the DC area found that of 200 prescriptions written for chlamydia or pelvic inflammatory disease only 57% were actually filled. Patients were more likely to fill scripts if they were hospitalized, which may reflect greater symptom severity or parental involvement. 
JAMA Peds

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Brush up

Acute COPD exacerbation

You know acute COPD exacerbations (AECOPD) because you see them every day, but formal definitions can be tricky. In general, guidelines define AECOPD as onset of new symptoms combined with the need for additional therapy. Watch for dyspnea, cough, and increased sputum production. Response to initial treatment can itself be used as a metric of exacerbation severity. In addition to signs of impending respiratory failure, take extra caution with patients with significant cardiovascular comorbidities, confusion or drowsiness, or new physical signs like peripheral edema or cyanosis.

What's the evidence

For azithromycin in AECOPD? A 2019 RCT of 300 patients with AECOPD, significant smoking history, and ≥ 1 exacerbation in the previous year found that azithromycin, when added to systemic corticosteroids and antibiotics within 48 hours of admission and subsequently continued for 3 months, decreased time to first treatment failure (49% within 3 months) compared to placebo (60%). No benefits were seen for azithromycin treatment beyond 6 months. 

What your REI friends are talking about

Not to say spermbanks were ever a source of implicit trust, but DNA tests for children born via artificial insemination have shown that sometimes banks used a different donor than promised. For some parents, the information was revealed decades after the fact.

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We're off next week and will return June 21st. A huge congrats to our resident writers who are movin' on up!

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