Jan 25, 2019

Choose wisely

The story

You broaden your work appeal by adding more lines to your CV, and pharma companies broaden their market by finding new uses for existing drugs. Can SGLT2 inhibitors prevent cardiovascular disease?

The background

In the crowded field of hypoglycemic agents for type 2 diabetes (T2D), SGLT2 inhibitors stand out for their ease of use – the daily pills are well-tolerated and place patients at little risk of hypoglycemia – and pleiotropic effects. The meds, which increase glucose excretion from the kidneys, improved cardiovascular and renal outcomes in 2 large trials of patients with established CV disease: 2015’s EMPA-REG OUTCOME and 2017’s CANVAS. A move to the primary prevention setting, where patients are at high risk but have not yet had a CV event, was a natural next step. 

The study

DECLARE-TIMI 58 compared SGLT2-inhibitor dapagliflozin to placebo in 17,000 patients with T2D at high risk for atherosclerotic disease. After median follow-up of 4 years, no difference was seen in the rate of major adverse CV events (MACE), but dapagliflozin produced a lower rate of death or hospitalization for heart failure (4.9% vs. 5.8%) driven mostly by fewer hospitalizations. The treatment group also saw fewer renal events (4.3% vs. 5.6%). Some adverse events seen in other SGLT2 trials, including an excess risk of amputation and fracture seen in CANVAS, were not seen here, suggesting they may have been due to chance.

The takeaway

DECLARE is the largest SGLT2 trial to date and shows a strong benefit for dapagliflozin in heart failure and CKD. For T2D patients at high risk of atherosclerotic disease, GLP-1 agonists like liraglutide may be a better choice.

Say it on rounds

When you schedule vacation between gen med and the ICU

It's all about the right mix. Though most colonic bacteria are obligate anaerobes, previous trials of fecal matter transplant (FMT) in ulcerative colitis (UC) used aerobically prepared stool. An RCT of 70 patients with active UC found that 32% of patients who received FMT with anaerobically-prepared pooled donor stool achieved clinical remission at 8 weeks compared to 9% of patients in an autologous stool control group. The anaerobic treatment (one colonoscopy and two enemas) was given over 1 week and may be much more feasible than high intensity aerobic regimens (5 enemas per week for 8 weeks).

When your patient has 14 listed phone numbers

Here's hoping that one of them works. And here’s hoping your P. vivax patient will comply with 14 days of treatment with primaquine. The lengthy med regimen is necessary to eradicate dormant parasites in the liver but suffers from poor compliance. A phase 3 RCT of 520 patients with P. vivax malaria found that single-dose tafenoquine, a long-acting primaquine derivative, was similarly safe and effective compared to longer primaquine treatment. Tafenoquine can cause severe bleeding in patients with G6PD deficiency, and field-ready G6PD testing remains a barrier to widespread use.

When your pager could be anywhere

Let the search begin. About half of recurrent hormone-receptor positive breast cancers occur 5 years after initial diagnosis, so finding markers for late relapse is key. An analysis of 350 patients previously treated for high-risk localized disease found that identification of circulating tumor cells (CTCs) in the blood between 4 - 7 years after treatment was highly predictive of late recurrence. A positive CTC assay, which separates tumor cells from other blood cells based on epithelial surface markers (see technical video here), was associated with a 13-fold increased risk of recurrence within 3 years.

Brush up

Interstitial lung disease (ILD)

Lung exams shouldn't sound like snap, crackle, pop. Consider ILD in patients with a years-long history of dyspnea and dry cough or velcro-like crackles on physical exam. Work up includes spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), and a high-res chest CT. If no causative disorder is found, idiopathic pulmonary fibrosis can be diagnosed based on characteristic histological patterns seen on imaging, namely bilateral reticulations in the lower lung fields.

What's the evidence

For pharmacologic management of IPF? Two 2014 trials introduced new therapies that slow disease progression. Both nintedanib, a tyrosine kinase inhibitor, and pirfenidone, an oral antifibrotic, slowed the rate of forced vital capacity (FVC) decline by about 50% over the course of a year in IPF patients. The meds also reduce severe respiratory events like acute exacerbations and may have a small mortality benefit. Unfortunately, prognosis for IPF remains poor with a median life expectancy of about 4 years.

What your peds friends are talking about

Whoever said two heads are better than one never tried to separate craniopagus (joined at the cranium) twins. Here's a case report of the dramatic procedure that successfully separated two 10 months-olds, including pics from before and after.

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