The Hospital Readmission Reduction Program, which lowered Medicare payments to hospitals with high readmission rates, has accomplished its direct goal of reducing readmission rates. This study, appearing in JAMA, evaluates for potential unintended consequences. For the video version, click here.Read More
An embarrassment of riches this week as we got not one, but two randomized clinical trials evaluating the timing of dialysis initiation in acute kidney injury. Of course, the results don’t agree at all. Back to the drawing board folks. For the video version of this post, click here.
OK here’s the issue – we nephrologists see hospitalized people with severe acute kidney injury – the abrupt loss of kidney function – all the time. There is always this question – should we start dialysis before things get too bad, in order to get ahead of the metabolic disturbances, or should we hold off, watch carefully, and jump when the time is right? Several people – and, full disclosure, I’m one of them – have examined this question and the answers have been confusing. The question begs for a randomized trial.
And, as I mentioned, we have two. One, appearing in the Journal of the American Medical Association, says yes, earlier dialysis is better with mortality rates of 40% in the early arm versus 55% in the late arm. The other, appearing in the New England Journal of Medicine says there is no difference – mortality rates were 50% no matter what you did.
Figure 1: JAMA Trial - GO TEAM EARLY!
Figure 2: NEJM Trial - D'Oh!
Sometimes, rival movie studies put out very similar movies at the same time to undercut each other’s bottom line. So which of these trials is Deep Impact, and which is Armageddon? Which is Ed TV and which is the Truman show? Which is Jobs and which is Steve Jobs?
Figure 3: It's like looking in a mirror...
In this table I highlight some of the main differences:
The NEJM trial was bigger, and multi-center, so that certainly gives it an edge, but what draws my eye is the difference in definitions of early and late.
The NEJM study only enrolled people with stage 3 AKI – the most severe form of kidney injury. People in the early group got dialysis right away, and the late group got dialysis only if their laboratory parameters crossed certain critical thresholds. The JAMA paper enrolled people with Stage 2 AKI. In that study, early meant dialysis right after enrollment, and late meant dialysis started when you hit stage 3.
OK so definitions matter. The NEJM trial defined early the way the JAMA trial defined late. So putting this together, we might be tempted to say that dialysis at stage 2 AKI is good, but once you get to stage 3, the horse is out of the barn – doesn’t matter when you start at that point.
That facile interpretation is undercut by one main issue: the rate of dialysis in the late group.
See, one of the major reasons you want to hold off on dialysis is to see if people will recover on their own. In the JAMA study, enrolling people at stage 2 AKI, only 10% in the late group made it out without dialysis – and those people were dialyzed, on average, only 20 hours after randomization. In the NEJM study, using the more severe inclusion criterion, roughy 50% of the late group required no dialysis. To my mind, if 91% of the late group got dialysis, you’re not helping anybody – the whole point of not starting is so that you never have to start, not that you can delay the inevitable.
Regardless of your interpretation, these studies remind us not to put too much stock in any one study. They should also remind us that replication – honest to goodness, same protocol replication – is an incredibly valuable thing that should be celebrated and, dare I say, funded.
For now, should you dialyze that person with AKI? Take heart – there’s good evidence to support that you should keep doing whatever you’ve been doing.
A 柚子 a day keeps the doctor away? Appearing in the New England Journal this week is a juicy study that suggests that consuming fresh fruit once daily can substantially lower your risk of cardiovascular disease. In fact, the study suggests that 16% of cardiovascular death can be attributed to low fruit consumption. For those of you keeping score, that's pretty similar to the 17% of cardiovascular deaths that could be prevented if older people stopped smoking.
For the video version of this post, click here.
What we're dealing with here is a prospective, observational cohort of over 500,000 Chinese adults without a history of cardiovascular disease. At baseline, they were asked how often they consumed a variety of foods, and gave a qualitative answer. Most of the analyses compare people eating fruit "daily" to those who ate fruit "rarely or never".
Those fruit-eaters were substantially different from the non-fruit eaters, but not, perhaps, in the way you might expect. For example, waist circumference and BMI were higher in the fruit-eaters and fruit-eaters were much more likely to live in urban rather than rural areas. Fruit-eaters also ate more meat, all suggesting that, in China at least, eating more fruit might be a marker of better nutrition overall. Reporting the cardiovascular effects of more frequent eating of other foods would reveal whether this is the case, but that data was not shown.
More in line with our Western expectations, fruit-eaters had a substantially higher income, more education, and were less likely to smoke or drink alcohol.
After more than 3 million person-years of follow-up, there were 5,173 cardiovascular deaths. If you followed a group of 1000 fruit-eaters for a year, you'd expect less than 1 cardiovascular death. Following a similar-sized group of never-fruit eaters, you'd expect 3.7 deaths.
These observations withstood adjustment for socioeconomic factors, smoking, physical activity, BMI and consumption of other types of food, though unmeasured confounding always plays a role in dietary studies.
Why does it work? We don't know. Though the frequent fruit-eaters had lower blood pressure and lower blood sugar, these factors did not explain the protective effects of the fruit.
Indeed, maybe it's not something in fruit that is beneficial at all, but something that isn't. Like sodium. Fresh fruit isn't salty and salt-intake was not captured in this study. Missing data like that makes it hard to trust that the observed relationship is truly causal.
Still, there isn't much harm in advising patients to eat fresh fruit more regularly, which is I suppose, what makes studies like these so appealing.