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The article, entitled "Que. hospitals ill-equipped for C. difficile" when it was originally posted on October 26, 2004, and now, apparently, deleted, included this comment from Dr. Sandra Dial, a medical epidemiologist at McGill University in Montreal, Quebec, Canada:

"According to Dial, frequent use of acid reflux medication eliminates the stomach acid that would otherwise kill such germs when they find their way into patients."

Dr. Dial had been previously quoted in June, on the day after the end of the time when "health authorities had not informed the public about the hospital outbreaks, saying they wanted to evaluate the severity of the disease first," saying, "It clearly is something worse than we've seen before." Dr. Dial, an intensive care physician at the Montreal Chest Institute who researched the extent of city's outbreak, went on to say, "It's a new situation so I think patients should be made aware."

Calls to Proctor & Gamble, marketers and distributors of the widely-popular Prilosec OTC (a proton pump inhibitor), generated a call-back from Dr. Kurt Weingand, the Associate Director of Proctor & Gamble's Health Sciences Institute in Cincinnati, Ohio. After some initial confusion, he said he thought the call was about a recently-releases study that claimed to establish a relationship between the use of PPIs and increased rates of pneumonia.

The next day, Dr. Weingand was interviewed at length by this reporter on Etopia Media Medical News Network. In that interview, Dr. Weingand vehemently disputed the claim made in "Risk of Community-Acquired Pneumonia and Use of Gastric Acid–Suppressive Drugs," an article in the Journal of the American Medical Association whose conclusion was:

"Current use of gastric acid–suppressive therapy was associated with an increased risk of community-acquired pneumonia."

You can listen to that interview with Dr. Weingand at Proctor & Gamble by clicking here.

A call to AstraZeneca, manufacturers of proton pump inhibitors Nexium®, Prilosec®, and the Prilosec OTC® marketed and distributed by Proctor & Gamble, resulted in its saying that the issue of the about the relationship between PPIs and C. diff., as raised by a Canadian doctor working with Canadian patients in Canadian hospitals, should be addressed to AstraZeneca Canada (notice that its web site features a "Nexium purple" motif).

A phone request to AstraZeneca Canada for comment resulted in an e-mail from its Primary Care Marketing department in Mississauga, Ontario, Canada, stating that:

"As the questions surrounding PPI use and c. difficile are a class issue, we are referring all media inquiries to the Canadian Association of Gastroenterology (CAG). There phone number is [number deleted] and can be found on the web at http://www.cag-acg.org/home.htm."

A call to the Canadian Association of Gastroenterology (CAG) in Oakville, Ontario, generated a promise of a just-released white paper directly addressing the issues raised by Dr. Dial's comment about the relationship between proton pump inhibitors and increased incidence of c. diff.. Asked during that call about the composition and membership of the Canadian Association of Gastroenterology, the organization's spokesperson indicated that it consisted of professional practitioners in the gastroenterological area, but not drug companies.

A graphic on the CAG site (now apparently inaccessible), however, indicated that 7% (by number) of the members of the CAG were drug companies. Information still posted on the site indicates that the CAG has a number of "Sponsors."

The highest level of sponsor is "Benefactor." Included in this category are:

Abbott Laboratories Ltd.
AstraZeneca Canada Inc.
Axcan Pharma Inc.
Janssen-Ortho Inc.
Pfizer Canada Inc.
Proctor & Gamble Pharmaceuticals

Benefactors prominently post their logos with links to their web sites on the CAG Sponsors web page here. They also are entitled to display their logos and links at the top along the right side of the CAG home page, here.

No specific dollar amounts of the contributions of these multi-billion dollar transnational pharmaceutical corporations to the operations of CAG and/or the salaries of its staff and officers are contained on the site. There is, however, this note at the bottom of the Sponsors list:

"The Association would like to recognize and thank our Corporate Sponsors as listed above. Corporate sponsorship provides funding which is essential for the day-to-day operation of the CAG, inclusive of National Office expenses and support for orphan programs not funded by other sources."

CAG goes on to say:

"In addition, many of our corporate sponsors are also generous supporters in the following areas:…one to three years of research funding to promising young pre-clinical and clinical scientists working in gastrointestinal health and disease…Canadian Digestive Diseases Week is the annual education event of the CAG, and one that would not be possible without financing from our corporate partners. Partners may choose from various sponsorship options including basic science and clinical symposia, small group breakfast sessions, paper and poster sessions, the prestigious McKenna lecture, research and education award lectures and the postgraduate course. The Association would like to thank our six Gold, one Silver and nine Bronze level sponsors of CDDW 2004."

In its Clostridium difficile Associated Diarrhea (CDAD) and Proton Pump Inhibitor Therapy: Position Statement,", the Canadian Association of Gastroenterology makes several major points:

1. Proton pump inhibitors are safe and effective medications
2. Only evidence-based and appropriate utilization of PPI's should be encouraged and this will lead to their cost-effective use
3. Recent exploratory data suggest a possible association between the use of PPI's and Clostridium difficile infection in a selected subgroup of hospitalized patients
4. The risks and benefits of administering, or discontinuing a PPI for a given patient needs to be carefully assessed on a case-by-case basis
5. The Canadian Association of Gastroenterology encourages its members, and indeed all health professionals, to keep abreast of any additional publications of relevant data

In Point 3 above, the author of this ”Position Statement" attempts to minimize and refute the contention that overuse, or use, of PPI's can increase the incidence of C. diff. infections, by going all-out in his or her use of qualifiers to diminish the significance of the "recent exploratory data" ( "Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case–control studies," by Dr. Sandra Dial and others, published July 6, 2004, in the e-Canadian Medical Association Journal and, in more discursive form with quotes from Dr. Dial, in "Drug combination linked to Clostridium outbreaks--Canadian researchers have found a connection between C. difficile cases and use of antibiotics with proton pump inhibitors," which appeared in the June 28, 2004, issue of amednews.com).

The subliminal message that there's nothing to worry about here is driven home in almost every word of the sentence: "Recent exploratory data suggest a possible association between the use of PPI's and Clostridium difficile infection in a selected subgroup of hospitalized patients."

The not-very-subtle subtext here is that if you're not hospitalized, not in a subgroup, not selected, then there is only a possible association hinted at in these exploratory data about which you need to worry, even though, as Dr. Dial says in the article above, ""God gave you acid in your stomach for a reason, and one of the things your stomach acidity does is kill bacteria for you," she said. "There are clearly people who need to be on these drugs, but not everyone who has heartburn needs them. We need to be careful about all the medications that we use."

In the interest of being fair and balanced, it should also be noted that the same article includes these comments:

"Dr. Dial's research team reviewed the medical records of more than a dozen hospitals in the area, finding more than 1,400 patients who tested positive for the bacteria in 2003. The team also linked 79 deaths to C. difficile. Researchers' analysis found that those who had received antibiotics and used PPIs were more than twice as likely to become sick.

"It's the combination of the two," said Dr. Dial. "If you only take [PPI's] and no antibiotics, your risks are very small."

This bullet point in the "Position Statement" is followed up with these details:

"Although limited [bolding added] data to date have shown that decreased gastric acidity leads to prolonged C. difficile organism or toxin survival or to other infectious diarrheal illnesses, a very recent report suggest that PPI utilization is associated with community acquired pneumonia." We all know by now that this refers to the JAMA-published study by Dr. Robert J. F. Laheij ("lay-hee"), discussed at length in Etopia Media Medical News Network #42.

But how, as the author seems to be trying to suggest, does the existence of "a very recent report" suggesting that "PPI utilization is associated with community acquired pneumonia" have anything to do with, let alone undermine, the point in the first half of that sentence that "data to date have shown that decreased gastric acidity leads to prolonged C. difficile organism or toxin survival or to other infectious diarrheal illnesses"?

The Laheij study was exhaustively denigrated yesterday by a Procter & Gamble (whose Canadian subsidiary, Procter & Gamble Pharmaceuticals Canada Inc., is a "Partner" level sponsor of this "Position Statement") spokesperson, who called the results of the Laheij study "hypothesized," "weak at best," and "not news."

Here, the impartial and public-spirited author from P&G (oops, CAG) calls the results of the study published by Dr. Dial and her colleagues on July 6, 2004, "retrospective," "based on limited data that do not take into consideration a number of important variables relating to hygiene practices," and claims that "the analyses may not have adequately accounted for other known confounding variables."

The author goes on to, in a manner of speaking, blame the victim, by calling attention to the fact that those most at risk tended to be older, sicker, and "were also prescribed antibiotics," implicitly arguing that since "in only 1 of 94 cases did the patient develop C. difficile infection on a PPI while off antibiotics" and because there is as of yet "no published data establishing an association between PPI use and C. difficile infection in an out-patient setting," there's really nothing to worry about.

All this disputation is, of course, part of the necessary and useful back-and-forth intrinsic to the practice of modern medical science, but the similar tone and vocabulary of both P&G's Dr. Weingand and the CAG author might reasonably raise some suspicion that, in addition to legitimate and appropriate caution in accepting the conclusions of these studies, there's also perhaps a bit of shared "spin" at work, in both cases on behalf of the companies paying their salaries.

(While carefully checking the footnotes in the CAG "Position Statement' is beyond the scope of this article, it should be noted that footnote 42, said to refer to "PPI use in an American case-control study," [Cunningham R, Dale B, Undy B, Gaunt N. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea (note the British spelling). J Hosp Infect 2003; 54:243-5], actually seems to be have been conducted, according to the abstract of this July, 2003, article on the PubMed web site, at the "Plymouth Public Health Laboratory, Derriford Hospital, Plymouth, UK.")

The document goes on in this vein for some while longer, at all times making the case that any conclusions about the connection between the use of PPIs and increased risk of C. diff. infection should be considered spurious, on the grounds that the apparent connection, or apparent causal relationship, is an artifact of "the type of patients affected," "the actual bacterial strain involved," or some "region-specific" cause.

The author also remarks that "Quinolone resistance has been raised as a possible additional issue," even though, according to a chart accompanying a very good discussion of the treatment of C. difficile induced diarrhea (CDIC) published in the late 1990s, quinolones are among the "least common" antibiotic agents to be implicated in CDIC and even to the extent that they are, what does the question of their being raised (in a passive voice) as "a possible additional issue" have to do with any causal relation between use, or overuse, of PPIs and increased risk of C. diff. infections, or with the price of tea in China, for that matter?

That this "Position Statement" of the Canadian Association of Gastroenterology speaks authoritatively in the name of that country's gastroenterology specialists, while being paid for by the drug companies who make billions selling PPIs to hospitals and consumers, may itself, in the language of these studies, warrant further investigation.