C. diff dangerous in ESRD but so is inaccurate reporting

Here are the first three paragraphs of a story from the medical news site, MedPage Today.

"ORLANDO – Patients on kidney dialysis who are infected with Clostridium difficile appeared to have a greater risk of infection relapse and also appeared to have a higher all-cause mortality that patients who do not have kidney disease, researchers said here.

"Mortality related to C. difficile infection was 3.8% among the 104 patients with end-stage renal disease (ESRD) and 1.46% among 300 controls without ESRD, said Massini Merzkani, MD, resident in internal medicine at the Albert Einstein School of Medicine's Jacobi Medical Center in Bronx, N.Y. (No data as to significance were presented.)

"In his poster presentation at the National Kidney Foundation 2013 Spring Clinical Meetings, Merzkani told MedPage Today that the relapse rate in severe C. difficile infection was 34.7% in the controls and 45.2% in the patients with ESRD. (No data as to significance were presented.)"

Does it make you nervous that "No data as to significance were presented"?

It should.

The authors didn't analyze the data for statistical significance. Would there be any way to do it yourself?

Yes, if you knew which statistical test to use.

Should a science reporter know something about statistics?

Yes, and the story was reviewed by an emeritus professor of medicine at an Ivy League medical school who should have known too.

In addition, there is a rather interesting math error. The mortality rate of 1.46% for the 300 controls doesn't compute. [300 x 0.0146 = 4.38] Unless 4.38 people died, the figure must be wrong.

Since both the mortality and relapse rates are categorical (yes or no) variables, the correct statistical test to use is Fisher's exact test.

The p value for mortality is 0.21 and for relapse is 0.061. Neither difference is statistically significant which means that based on this study, one cannot say that "C. diff is dangerous in ESRD."

You might point out that a p of 0.061 is pretty close to the magical value of 0.05. That is true, but there is another major flaw in the study. The article says the ESRD patients "were compared with patients without chronic kidney disease who were admitted with C. difficile infection during the same time period. The researchers calculated that randomly selecting 300 of the 2,400 control patients would produce a valid comparison of outcomes."

Despite that "calculation," the comparison is invalid. One cannot simply compare ESRD patients to random patients. They would at least need to be matched for age, sex, co-morbidities other than ESRD and perhaps other variables to eliminate confounding.

It is possible that ESRD patients will have worse outcomes if they contract C. diff colitis. But this study doesn't prove that, and the story is misleading.

It's 2013. I agree with The Guardian's Observer column which says that Nate Silver's accurate predictions highlight "the importance of statistical literacy in our data-heavy age."

Overuse of proton pump inhibitors is expensive & dangerous

Let’s talk about proton pump inhibitors [PPIs]. These drugs, successors to the innovative H2 blockers, have revolutionized the treatment of gastro-esophageal reflux disease [GERD] and peptic ulcers.

But like all good things, too much can be a problem, and that’s where we are today.

A new study shows that of 90 patients who were tested and found NOT to have GERD, 38 [42%] continued to take PPIs which had been prescribed prior to the testing. Some apparently were not always told to stop the medication and others continued it because they remained symptomatic.

Ambulatory patients are not the only ones overusing PPIs. According to UpToDate, the indications for stress ulcer prophylaxis in hospitalized patients are as follows:

Mechanical ventilation for more than 48 hours, coagulopathy, GI ulceration or bleeding within the past year, traumatic brain injury, traumatic spinal cord injury, severe burns, or two or more minor risk factors, including sepsis, ICU admission lasting >1 week, occult GI bleeding lasting ≥6 days, or high-dose glucocorticoid therapy.

But in most hospitals, intravenous PPIs are routinely ordered for any patient who is npo [not taking food or drink by mouth]. There is not one shred of evidence that PPIs are indicated in this setting. I am old enough to remember the days before PPIs and H2 blockers existed. I assure you that millions of patients were npo and did not develop gastritis or ulcers.

Of course, PPIs are available over the counter [OTC] now, and although they are meant to be taken for only 3 weeks at a time and for no more than 3 such courses per year, there is really no limit to the number of PPIs purchased and used.

In 2010, an estimated $11.4 billion of prescription PPIs alone were sold. The amount of OTC drugs sold is not included, but Consumer Reports noted that in 2009, Nexium OTC sales amounted to $6.3 billion.

Among the adverse effects associated with PPIs reported in a recent systematic literature review are these:

Clostridium difficile-associated diarrhea

Community-acquired pneumonia

Osteoporotic fracture

Vitamin B12 deficiency

Inhibition of antiplatelet therapy

Other studies show that hospital-acquired pneumonia may also be more frequent in patients on PPIs.

Many experts feel that the current epidemic of C. diff colitis is being fueled not only by the indiscriminate use of antibiotics, but also by the overuse of PPIs.

How can the overuse of PPIs be stopped? When I was teaching residents, I tried to confront them with the evidence of harm and lack of evidence of utility of PPIs for patients who were simply npo. It didn’t seem to matter. Someone or something had gotten into their heads, and I couldn’t convince them.

I can’t count the number of outpatients I see who say they are on PPIs for GERD or “gastritis” but have never had a proper workup to establish those diagnoses. I have no idea how to stop the wholesale use of PPIs by primary care MDs, gastroenterologists and people who self-medicate.

It may be hopeless.