Much has been touted in the media and social media about the recent proton pump inhibitor (PPI) study in JAMA relating long term use of these drugs to chronic kidney disease.  There is so much hype that I thought it important to take a closer look.

The study in JAMA is only available to the public as an abstract, which means the authors condensed an 8 page document into 7 paragraphs (basically a half-page).  This is standard…you  have to PAY to be able to read the whole article, and the abstract doesn’t tell the whole story.   Your old pal, an individual who cares about his listeners, arranged to get a full-text copy of the article so we can go over the “numbahs” together.

First, this is a “cohort study” and it’s “retrospective” and therefore “observational.”  This means they took a ton of people who were in another study (Atherosclerosis Risk in Communities (ARiC)) and teased out information they weren’t originally looking for out of the data after the fact.   Basically you take 10,000 or more people and find the ones on long term PPIs and see how many developed kidney disease (and how you define that matters) and compare them against all the people in the group who DIDN’T take PPIs and see if there’s a difference.   This is a decent study, as far as cohort studies go, but when we look at levels of evidence, we see that this kind of study isn’t the best for proving a scientific point:

There are two levels of evidence above cohort study that are generally considered to result in better quality, and therefore more believable, results.  Performing a double blind, placebo controlled study comparing kidney disease rates in PPI vs Non-PPI users would take another 10 or more years to complete, so this is the best data we have right now (and it’s decent, as I said.)  So let’s go with it.

There were 10482 participants in the ARiC study.   Since this study was not designed to look at PPI use initially (the data was gathered as part of a general information gathering system regarding the patients enrolled), there were some lopsided aspects to the PPI group.  For example, the PPI users were more often obese, white, and hypertensive than the non-PPI users.  This is the kind of thing that can cause bias to creep into a study (hypertensive patients are more likely to develop kidney disease, for example) that would be eliminated from a randomized, control trial.

Of the 10482 participants, there were 1438 cases of chronic kidney disease identified (13.7%).  There were 56 events in the PPI group (of which there were 322 users), amounting to 17.4% (0.174).   In the non-PPI group, 1382 out of 10160 patients developed kidney disease, or 13.6% (0.136).   You can spread this out into patient-years and all kinds of things, but we can see that there is a higher percentage of kidney disease in the PPI group than the non-PPI group, and the difference is 17.4/13.6 or a 27.9% increase.  (They used another cohort to confirm these results and make the data more powerful.)

This is where the headlines come from: “A 30 PERCENT INCREASE IN KIDNEY DISEASE IN PPI USERS!”

So that certainly seems to be “true,” in the sense that to the best of our knowledge, there is an increased risk of chronic kidney disease in people who take PPIs for years and years, but what does that mean for the individual?  And does this make PPIs “bad drugs?”

To figure this out, we need to review the difference between absolute risk and relative risk.

If you have 1000 people in a treatment group and 1000 people in a placebo group, and 10 people have an adverse reaction in the treatment group and only 7 have one in the placebo group, you could say that there is a 30% increase in that adverse reaction in the treatment group.  But the ABSOLUTE increase was only 3 patients out of a thousand so the absolute risk to the individual would be 3/1000 or 0.003 or 0.3%.   In addition, we can take the inverse of this number to figure out the “Number Needed to Harm(NNH)” (i.e., how many people have to take the drug to have one excess incident of the adverse effect), which in this case would be 333.  So the risk to the individual is quite low;  your odds would be 332 to 1 of NOT getting the adverse event.  Another way to look at it is that 99.7% of the time you’d be ok.

Let’s apply this to the case at hand:  The absolute risk of developing chronic kidney disease from taking chronic PPI is 0.174-0.136=0.038.  Therefore the Number Needed to Harm is 1/.038, or 26.  So the risk to you, the individual, taking a PPI for years and years and years, and developing chronic kidney disease associated with PPI use is 25 to 1, or 3.8%.  In other words, you wouldn’t get PPI-associated CKD (assuming this effect is real) 96.2% of the time.  We can look at it another way:  the risk to the individual is very low, but the risk to society (factor that Number Needed to Harm into the MILLIONS of people taking PPIs every year) is greater.   Additionally, this data is from 1996 to 2011, and newer PPIs that were not included may not even have this same effect.

There are other adverse effects from decreasing acid production in the stomach…there may be an increase in bacterial illnesses due to the decrease in bacteria-killing hydrochloric acid in the stomach.  There have been suggestions of increased bone fractures in elderly patients who take PPIs chronically, but the NNH is greater than 1200 on that one and may be erroneous.

The flip side of this is that PPIs are very, very effective at what they do.  The Number Needed to Treat for total healing of erosive esophagitis is 6.  The Number Needed to Treat to reduce GI rebleeding (preventing recurrence after a first GI bleed) is 13.  We used to see dozens of vagotomy/antrectomy procedures a year in a decent sized hospital before the advent of H2 blockers (e.g., ranitidine) and PPIs…I believe we saw ONE in our institution last year and that was for someone with a genetic predisposition to overproduction of acid.   So PPIs have reduced surgery rates and concomitant surgical complications.  In addition, quality of life is improved in patients on PPIs, but only under certain circumstances.  PPIs are still “Generally Considered Safe.”

There are adverse effects with every medication (google the number of deaths from acetaminophen last year for an eye opener).  Proper medical treatment involves balancing risk vs benefit.  Proper medical treatment also dictates that people be treated for the proper indication.  It is estimated that 20-70% of people who take PPIs take them without a proper indication.  In addition, being OTC, these medications can be taken for years without a healthcare provider’s supervision.

Lifestyle measures may help a significant fraction of heartburn sufferers treat their symptoms without medication.  For refractory cases, primary care and gastroenterologists have a full array of treatments, surgical, medical, and lifestyle to relieve symptoms and reduce adverse outcomes.  One of the most powerful weapons is still the proton pump inhibitor, so if you’re prescribed one for a proper indication, don’t fear it, just be aware of the risks and benefits and take it only as long as necessary and at the lowest effective dose.   Remember, the risk to YOU, the individual is low (but never zero).

yr obt svt,

Dr Steve

This is the paper Intern Jesse (now Associate Producer Jesse) had to turn in to his university to get credit for his rotation with us.  He did a great job, and deserved the solid C+ we gave him for his efforts.  🙂

Internship Reflection

“It’s Weird Medicine, the first, and still only, uncensored medical show in the history of radio!”  In the last few months, I’ve heard those words more times than I can count.  That one phrase, along with a hefty majority of the rest of the introduction, is burned into my memory.  I can recite SiriusXM channels, website URLs, promotional codes, and phone numbers without even thinking about it.  I’m not complaining, though.  Not by a long shot.

This semester I had the great fortune to intern with Weird Medicine, an established SiriusXM show and podcast on the Riotcast Network, as an assistant producer.  Each week, I met up with Dr. Steve and the rest of the Weird Medicine crew and we recorded the SiriusXM show for that week.  Once a month, we’d all get together at the studio and record enough podcasts to get us through till the next month.  It could be a lot of work sometimes, but I wouldn’t have traded it for anything.

I’m not really sure what I can say that would adequately describe my working with Dr. Steve and the Weird Medicine crew that would also fill up three pages.  Each time I walked into the studio was extremely different than the last.  I had no idea what questions were going to show up that day, whether they be about some devastating illness, the many, many problems that I learned that people can have with their assorted genitalia, or even people calling in just to say hello or to throw in some obscure reference to an Opie and Anthony episode from however many years back that would leave everyone in stitches.  I’ve gotten a lot more practice mixing audio and learning the importance of compressors for broadcast audio.  I’ve screened calls, looked up the Material Safety Data Sheet (MSDS) for obscure chemicals, monitored UStream chatrooms during our live tapings, and made multiple “Best Of” shows for both the podcast and the SiriusXM show.  All in all, the entire experience was a lot of fun and I learned so much from it.

One of the things that I learned during my time with Weird Medicine is the importance of the various social media platforms that we have at our disposal.  Dr. Steve has so many people tweeting at him every day that I was honestly surprised that checking the Twitter wasn’t one of my duties.  Still, he manages to reply to almost every single tweet that gets sent to him every day.  The same goes for any questions posted to the Weird Medicine sub-Reddit and any emails or text messages that his listeners send to him.  He’s made it a point to build a community around these shows, and these people are all united in a way.  People are sharing links to different scientific studies, they’re answering each other’s’ questions or helping point them in the right direction.  They have regular listeners that call in frequently and regular listeners that might not call in, but they’re always there in the UStream chatroom for the live recordings.  No one is judging them for asking for help from some random doctor on the radio, and everyone acts like they’re friends with everyone.  Don’t get me wrong, there are also jokes at each other’s expense, but that’s what friends do.  Right?

As someone who looks at podcasting as a possible career choice, seeing the way that Dr. Steve has built this community around these shows shows me just how important social media is.  In fact, I’ve become quite a bit more active on Twitter since I started the internship and have interacted with the Weird Medicine community quite a bit myself.  I even used a lot of their input when I was building the first “Best Of” show that I made for Dr. Steve.  Believe me, there were a lot of people that were more than willing to tell me the funniest thing they’d ever heard on the show just so I could make sure other people got to listen to it, too.

As I said before, the whole experience was great fun and I learned a lot from it.  Not only that, but I’ve also made some connections with some great people.  Aside from the Weird Medicine crew, I’ve also interacted with another couple of podcasters and even gotten a shout out on one podcast for the work that I put in on my “Best Of” shows.  All in all, I’m so glad that I had this opportunity come my way, and I look forward to helping Weird Medicine and Doctor Steve by producing some more things for the show in the future.

Well, our friend on Twitter @SonOfFritz gave us this artwork for the whistling rectal rocket  novelty item, being produced by our friend Danny in Canada.   If the dumb things never make it to market, this cover art made me very, very happy.

Our friend, Tracy DeMarzo (many of you know her as Rick Shapiro’s wife) is battling breast cancer and has a GoFundMe account for her surgery and reconstruction.   To quote Tracy:

For those of you that know me, you know that I have great self-body-image. And yes, many of you have seen my boobs! Which makes me love them more.  I have been on stages as a stripper, I have been to Fantasy Fest in Key West, wet t-shirt contests, naked piano dancing.. it was all me. But more importantly, my breasts have given me access to great self body image has lent hand in my confidence, my self-esteem.. and more so, my ability to love myself.

I am seeking enough money to see a specific Doctor. Any monies raised additionally will go to charity. As well, I will be participating in a photo-shoot which will carry the Breast Cancer logo and I am hoping to auction those off, signed. My last hope is to organize a comedy show all about boobs.

You all know our position on Weird Medicine, we support boobs under all circumstances, and friends’ boobs are even more important.

Please give $1, $5, $100, whatever you can give for this worthy cause (and I’m pretty sure Tracy will show us her new anatomy when she’s done!)

Cancer sucks.   I don’t guess I’m going too far out on a limb, saying that.  🙂  CLICK HERE TO DONATE TO TRACY’S TITS.

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Dr Steve

It is with great sadness that I report that our friend of many months, RexDart, AKA Jeff Zurio, succumbed to his metastatic cancer earlier in the month.  Fred from Brooklyn and I had kept in touch with him and when I last spoke with him he was in good spirits with good pain control.  He had friends in El Paso who were going to actually care for him so he wouldn’t be alone.   After that phone call, we lost all contact with Jeff.

One thing Jeff told me (many times, actually) was that the support, both financially and emotionally, from Weird Medicine, O&J and interrobang.com fans was the only thing that kept him going his last few months.   Thank you all for being such great, great people;  this shows that even a little effort by a lot of people can ease suffering and improve quality of life in people that we’ve never even met.  Amazing.

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Steve

We have a listener who has been battling terminal bladder cancer since 2011. He’s had to try to continue to work just to keep the lights on despite horrific intractable pain, but hasn’t had a full time job since being laid off in 2012. A few months ago he told me “i’m already $100 away from being homeless. At this point I long for the relief that death will bring.”

Recently he was admitted with intractable bleeding from his bladder, causing blood clots that obstructed his urethra, causing horrific pain. A large catheter with three tubes in it did continuous irrigation to clean his bladder out. Being admitted wiped out his account and he has $1000/month in bills on a $700/month income.

He has no family who can help him, and he’s alone, suffering in a cold house trying to live on $700 a month. He finally has an oncologist who will TRY to treat him, but the chemo is keeping him from working and he just got admitted to the hospital with a blood sugar of 700.

He got better for awhile and we stopped raising money for him; he’s again bed ridden and can’t work. Eventually he will need hospice but the docs think they might be able to kick this thing back a bit if he can just make it to the treatments and stay out of the hospital.

Please donate below, $5, $10, $100, whatever you can afford; 100% will go to RexDart who is known to people on the Interrobang website and on twitter as @rexdart936.

Let’s see what we can do as a group to keep the lights on and some heat going so our friend can live out his days in peace.