Oltipraz is a drug that was originally used to treat intestinal worms. It was later found to prevent a broad variety of cancers (1). This was attributed to its ability to upregulate cellular detoxification and repair mechanisms.
Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.
A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.
The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.
This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.
Oltipraz
Oltipraz is a drug that was originally used to treat intestinal worms. It was later found to prevent a broad variety of cancers (1). This was attributed to its ability to upregulate cellular detoxification and repair mechanisms.
Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.
A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.
The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.
This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.
Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.
A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.
The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.
This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.
IOM Committee on Patient Safety and Health IT, Meeting Two: Institute of Medicine, or of Mediocrity?
In my Jan. 2011 post "Institute of Medicine Committee on Patient Safety and Health Information Technology, and Thoughts on Social Aspects of Health IT Evaluation" I wrote that:
Here are links to the PPT presentations from Meeting 2 of the Committee on Patient Safety and Health IT that took place Feb. 24, 2011:
The PPT's can be downloaded directly from these links.
I note several observations:
The IOM's rules of engagement, according to the Study Director, preclude my testifying, as a Medical Informatics specialist and former CMIO, about a relative's nearly being killed by poorly designed and implemented health IT. Instead, the linked presentations above are presented.
Here's an example of what I consider a somewhat rigorous and critical thinking-based presentation on health IT risks:
I think the IOM should be able to do better than a mere small-university medical informatics adjunct professor.
-- SS
The U.S. National Research Council of the National Academy of Sciences issued a report in early 2009 on the state of health IT. That study's report, led in part by pioneers in Medical Informatics G. Octo Barnett and William Stead, was entitled "Computational Technology for Effective Health Care: Immediate Steps and Strategic Directions" (pre-publication PDF available free at this link). The report was announced under the following header:CURRENT APPROACHES TO U.S. HEALTH CARE INFORMATION TECHNOLOGY ARE INSUFFICIENT
The insufficiencies were largely in the areas of difficulties with data sharing and integration, deployment of new IT capabilities, large-scale data management, and lack of cognitive support by health IT for busy clinicians.
One might reasonably conclude such deficits could affect patient safety.
Recently the Institute of Medicine (the health arm of the National Academy of Sciences) formed a Committee to study health IT safety. It held its first meeting on Dec. 14, 2010 (quite a few years late in my opinion, and only after tens of billions of dollars have been earmarked for health IT, but better late than never):
The Institute of Medicine Committee on Patient Safety and Health Information Technology is holding its first meeting on December 14-15, 2010. The first day, December 14, 2010 beginning at 10:30 am, is open to the public to observe the committee proceedings. The committee will hear presentations by the Office of the National Coordinator and other invited guests. There will also be an opportunity for members of the public and representatives of interested organizations to make a brief statement before the committee. Prior registration is requested for attendees and required for those wishing to make a statement.
Here are links to the PPT presentations from Meeting 2 of the Committee on Patient Safety and Health IT that took place Feb. 24, 2011:
http://www.iom.edu/~/media/Files/Activity%20Files/Quality/Patient%20Safety%20and%20HIT/Meeting%202/Dwork.pdf
http://www.iom.edu/~/media/Files/Activity%20Files/Quality/Patient%20Safety%20and%20HIT/Meeting%202/WoodsNormanFeb2011.pdf
http://www.iom.edu/~/media/Files/Activity%20Files/Quality/Patient%20Safety%20and%20HIT/Meeting%202/Harper%20IOM%20HIT%20Patient%20Safety.pdf
http://www.iom.edu/~/media/Files/Activity%20Files/Quality/Patient%20Safety%20and%20HIT/Meeting%202/Chrisman-.pdf
http://www.iom.edu/~/media/Files/Activity%20Files/Quality/Patient%20Safety%20and%20HIT/Meeting%202/Palmer.pdf
The PPT's can be downloaded directly from these links.
I note several observations:
- The overall quality of these presentations appears mediocre;
- Issues of healthcare IT risks - as they exist on the ground in 2011 - are addressed poorly if at all;
- Proposed "solutions" are really nothing novel or new compared to existing literature or recommendations made in earlier studies, including that of the US NRC;
- That these presentations come from the highest scientific body in the United States is, in my opinion, a disappointment and, indeed, an embarrassment.
The IOM's rules of engagement, according to the Study Director, preclude my testifying, as a Medical Informatics specialist and former CMIO, about a relative's nearly being killed by poorly designed and implemented health IT. Instead, the linked presentations above are presented.
Here's an example of what I consider a somewhat rigorous and critical thinking-based presentation on health IT risks:
http://www.ischool.drexel.edu/faculty/ssilverstein/Clinical_IT_benefits_risks.ppt
I think the IOM should be able to do better than a mere small-university medical informatics adjunct professor.
-- SS
Once More with Feeling: Another Defense of Conflicts of Interest Based on Logical Fallacies
Despite increasing recognition of the adverse effects of health care professionals' and health care institutions' conflicts of interest on health care, such financial relationships continue to have their prominent defenders. The latest example was an article in Medscape General Surgery by Frank J Veith MD, entitled "Physicians and Industry: Fix the Relationships, but Keep Them Going." Dr Veith is a prominent vascular surgeon who "received numerous awards and honors as a leader, outstanding teacher, and innovator in vascular surgery," according to New York University
We have noted before how defenders of conflicted professionals and professional societies often employ logical fallacies to support their arguments. Some recent examples were discussed here, by a prominent ostensibly libertarian attorney and law professor; here, published in a well-known medical journal by the former director of "medical communications" for a large pharmaceutical firm; and here, by the president of a large medical society, published again in a well-known medical journal.
Dr Veith seems to be continuing that tradition. His approach emphasized frequent repetition of the same fallacious argument.
Straw Man: "Totally Interrupt All Doctor-Industry Relationships"
Dr Veith's main argument seemed to be with attempts to prevent physicians from having any relationships with industry, presumably including not just financial relationships, but professional collaborations or even personal friendships. For example, he wrote about
Furthermore,
Then later, Dr Veith wrote,
Finally, he concluded thus,
Despite making this argument at least four times, the problem is that Dr Veith provided no citations, much less evidence that such "draconian" policies have been enacted or even advocated.
There have been new policies on conflicts of interest suggested or adopted by some organizations. None, to my knowledge have been exactly "draconian."
For example, Harvard University does have a new policy on conflicts of interest. Maybe Dr Veith was referring to it above when he mentioned Harvard. However, in an interview about the new policy involving university leaders published in the Harvard Gazette, the Vice Provost of the University said,
So Dr Veith's main premise seems to be based on a multiply repeated straw-man argument. He argued again and again against a policy that no one seems to be advocating. (And even I, as a hard-liner about conflicts of interest, have never advocated a complete interruption of all relationships of any kind between all physicians and all of industry.)
Appeal to Fear: You Will be "Blighted"
Perhaps just to spice things up, Dr Veith warned of the dire consequences of the "draconian" policies that no one was advocating:
Dr Veith had asserted multiple benefits of continuing relationships among physicians, health care institutions, and commercial firm. He presented no evidence to support his assertions, most of which can be questioned (see below). His warning that institutions will be "blighted" was based on his assertion that the stringent policy no one advocated would eliminate these unproven benefits, hence his warning of something so severe as "blight" seemed to be an appeal to fear.
Ad Hominem: "Sanctimonious" Physicians Leading a "Witch Hunt"
As noted above, Dr Veith referred to anonymous physicians who "sanctimoniously jumped on the bandwagon," thus leading to
And again,
My interpretation is that this was an implied set of ad hominems. Those who supposedly advocated the "draconian" policy were made out to be "sanctimonious" witch hunters. After just having seen "The Crucible," I could also argue that the use of the term "witch hunt," with its current extreme emotional references (apparently to a case in which presumably innocent people were hanged), amounted to an appeal to emotion and an appeal to fear.
Summary
I must admit Dr Veith's entire set of arguments was not completely based on logical fallacies. However, the rest of his arguments hardly appeared even-handed. He presented a series of assertions about the benefits of such relationships, including that they "foster innovation and development," that "industry-sponsored medical education helps to keep physicians informed about new developments," that industry sponsored education about devices prevents "difficult and dangerous" practices, and helps physicians use devices "better and more safely." He provided no evidence in favor of these claims, and seemed to ignore arguments about the hazards of payments to physicians biasing their clinical practice, teaching and research.
I should also note that these arguments were made by a physician who appears to have his own personal financial relationships with industry. In the Medscape article, Dr Veith "disclosed no relevant financial relationships." However, as a member of the editorial board of Medscape General Surgery, Dr Veith "disclosed the following relevant financial relationships: Owns stock, stock options, or bonds from: Vascular Innovations, Inc." Furthermore, the disclosure summary for the iCON2011 conference includes the following for Dr Veith, "Honorarium/Expenses: Cook Medical, Cordis, WL Gore, Medtronic." Finally, Dr Veith apparently runs the Veith Symposium, which in 2010 acknowledged the following commercial sponsors: Aastrom, Abbott Vascular, Aptus Endosystems Inc, Atrium, Bard Peripheral Vascular, Boston Scientific, Cook Medical, Cordis Cardiac and Vascular Institute, Delcath Systems Inc, Gore, Hansen Medical, Lombard Medical Technologies, Maquet, Medtronic, Organogenesis Inc, Sanofi-Aventis, St. Jude Medical, Tenaxis Medical, Triavascular, Vascutek Terumo.
So Dr Veith's article continues the tradition of defenses of physicians' and health care institutions' conflicts of interest based on logical fallacies and unbalanced and unsupported assertions. Also, note that all the examples of such defenses we have discussed were made by people with their own financial relationships with drug, device, and/or biotechnology companies, although some of them disclosed these relationships. I have yet to see a defense of such conflicts based on logic and evidence, or a defense of such conflicts made by someone who has absolutely no conflicts of his or her own.
The currently prevalent relationships with health care corporations among academic physicians, researchers, and other decision makers and influencers in health care have been lucrative for them. I have yet to see a coherent, logical argument that these relationships are good for patients, medical education, biomedical or clinical science, or public health made by anyone, much less someone who does not have such relationships.
I will note that the defenses of conflicts of interest begin to seem drearily similar. Not only do they often use the same logical fallacies, but they repeat the same stale and unsupported arguments about the benefits of financial relationships with industry: that they foster "innovation," and that they provide better educational opportunities than unconflicted programs and educators. We now know that the managed care industry has engineered stealth health policy advocacy campaigns that furnish talking points to "third parties" which may get caught up in the larger policy discourse (see posts here and here). I wonder whether some such stealth health policy advocacy campaign by pharmaceutical, device and/or biotechnology companies seeded the discourse about conflicts of interest with some of the logical fallacies and unproven assertions that have become so familiar.
We need to elevate our discourse about health care policy. People involved in health policy discussions should at least disclose their conflicts of interest when making their points. We should be very skeptical of arguments and look carefully for the evidence and logic that supports them. When we find that evidence and logic is lacking, be even more skeptical about who benefits from them.
We have noted before how defenders of conflicted professionals and professional societies often employ logical fallacies to support their arguments. Some recent examples were discussed here, by a prominent ostensibly libertarian attorney and law professor; here, published in a well-known medical journal by the former director of "medical communications" for a large pharmaceutical firm; and here, by the president of a large medical society, published again in a well-known medical journal.
Dr Veith seems to be continuing that tradition. His approach emphasized frequent repetition of the same fallacious argument.
Straw Man: "Totally Interrupt All Doctor-Industry Relationships"
Dr Veith's main argument seemed to be with attempts to prevent physicians from having any relationships with industry, presumably including not just financial relationships, but professional collaborations or even personal friendships. For example, he wrote about
a recent initiative to completely sever the relationship between industry and doctors has gained traction. This initiative has been supported by several states, including Massachusetts and Vermont, and universities, such as Harvard, Stanford, the University of Massachusetts, and the University of Michigan, which have enacted draconian laws or policies designed to separate doctors and industry and to interrupt any relationship between them.
Furthermore,
Even many individual physicians have sanctimoniously jumped on the bandwagon and written articles or opinion pieces attacking the evils of any relationship between industry and doctors, suggesting the severance of any such relationships.
Then later, Dr Veith wrote,
We should establish rules to prevent or minimize the abuses, but we should not totally interrupt all doctor-industry relationships. To do so is wrong-headed and would eliminate the many beneficial effects that accrue to medical care and society from these relationships. It would be throwing the baby out with the bathwater.
Finally, he concluded thus,
These will be far better solutions than completely eliminating all industry-doctor relationships.... Such safeguards will be better than the present trend for institutions and governments to enact strict measures to separate physicians from industry.
Despite making this argument at least four times, the problem is that Dr Veith provided no citations, much less evidence that such "draconian" policies have been enacted or even advocated.
There have been new policies on conflicts of interest suggested or adopted by some organizations. None, to my knowledge have been exactly "draconian."
For example, Harvard University does have a new policy on conflicts of interest. Maybe Dr Veith was referring to it above when he mentioned Harvard. However, in an interview about the new policy involving university leaders published in the Harvard Gazette, the Vice Provost of the University said,
The University is not designed to be an ivory tower isolated from the world. So the trick is to be able to have a robust system for affording faculty opportunities to engage with the commercial world and at the same time not threaten in any way their own fundamental integrity or that of Harvard.That hardly sounds like a policy that completely severs all relationships between faculty and industry.
So Dr Veith's main premise seems to be based on a multiply repeated straw-man argument. He argued again and again against a policy that no one seems to be advocating. (And even I, as a hard-liner about conflicts of interest, have never advocated a complete interruption of all relationships of any kind between all physicians and all of industry.)
Appeal to Fear: You Will be "Blighted"
Perhaps just to spice things up, Dr Veith warned of the dire consequences of the "draconian" policies that no one was advocating:
Those institutions that choose such inquisitional approaches will be blighted and suffer competitive disadvantages.
Dr Veith had asserted multiple benefits of continuing relationships among physicians, health care institutions, and commercial firm. He presented no evidence to support his assertions, most of which can be questioned (see below). His warning that institutions will be "blighted" was based on his assertion that the stringent policy no one advocated would eliminate these unproven benefits, hence his warning of something so severe as "blight" seemed to be an appeal to fear.
Ad Hominem: "Sanctimonious" Physicians Leading a "Witch Hunt"
As noted above, Dr Veith referred to anonymous physicians who "sanctimoniously jumped on the bandwagon," thus leading to
The initiative to separate industry from physicians and surgeons [which] has taken on the trappings of a witch hunt.
And again,
Their leaders should recognize this and resist the temptation to join the separation witch hunt....
My interpretation is that this was an implied set of ad hominems. Those who supposedly advocated the "draconian" policy were made out to be "sanctimonious" witch hunters. After just having seen "The Crucible," I could also argue that the use of the term "witch hunt," with its current extreme emotional references (apparently to a case in which presumably innocent people were hanged), amounted to an appeal to emotion and an appeal to fear.
Summary
I must admit Dr Veith's entire set of arguments was not completely based on logical fallacies. However, the rest of his arguments hardly appeared even-handed. He presented a series of assertions about the benefits of such relationships, including that they "foster innovation and development," that "industry-sponsored medical education helps to keep physicians informed about new developments," that industry sponsored education about devices prevents "difficult and dangerous" practices, and helps physicians use devices "better and more safely." He provided no evidence in favor of these claims, and seemed to ignore arguments about the hazards of payments to physicians biasing their clinical practice, teaching and research.
I should also note that these arguments were made by a physician who appears to have his own personal financial relationships with industry. In the Medscape article, Dr Veith "disclosed no relevant financial relationships." However, as a member of the editorial board of Medscape General Surgery, Dr Veith "disclosed the following relevant financial relationships: Owns stock, stock options, or bonds from: Vascular Innovations, Inc." Furthermore, the disclosure summary for the iCON2011 conference includes the following for Dr Veith, "Honorarium/Expenses: Cook Medical, Cordis, WL Gore, Medtronic." Finally, Dr Veith apparently runs the Veith Symposium, which in 2010 acknowledged the following commercial sponsors: Aastrom, Abbott Vascular, Aptus Endosystems Inc, Atrium, Bard Peripheral Vascular, Boston Scientific, Cook Medical, Cordis Cardiac and Vascular Institute, Delcath Systems Inc, Gore, Hansen Medical, Lombard Medical Technologies, Maquet, Medtronic, Organogenesis Inc, Sanofi-Aventis, St. Jude Medical, Tenaxis Medical, Triavascular, Vascutek Terumo.
So Dr Veith's article continues the tradition of defenses of physicians' and health care institutions' conflicts of interest based on logical fallacies and unbalanced and unsupported assertions. Also, note that all the examples of such defenses we have discussed were made by people with their own financial relationships with drug, device, and/or biotechnology companies, although some of them disclosed these relationships. I have yet to see a defense of such conflicts based on logic and evidence, or a defense of such conflicts made by someone who has absolutely no conflicts of his or her own.
The currently prevalent relationships with health care corporations among academic physicians, researchers, and other decision makers and influencers in health care have been lucrative for them. I have yet to see a coherent, logical argument that these relationships are good for patients, medical education, biomedical or clinical science, or public health made by anyone, much less someone who does not have such relationships.
I will note that the defenses of conflicts of interest begin to seem drearily similar. Not only do they often use the same logical fallacies, but they repeat the same stale and unsupported arguments about the benefits of financial relationships with industry: that they foster "innovation," and that they provide better educational opportunities than unconflicted programs and educators. We now know that the managed care industry has engineered stealth health policy advocacy campaigns that furnish talking points to "third parties" which may get caught up in the larger policy discourse (see posts here and here). I wonder whether some such stealth health policy advocacy campaign by pharmaceutical, device and/or biotechnology companies seeded the discourse about conflicts of interest with some of the logical fallacies and unproven assertions that have become so familiar.
We need to elevate our discourse about health care policy. People involved in health policy discussions should at least disclose their conflicts of interest when making their points. We should be very skeptical of arguments and look carefully for the evidence and logic that supports them. When we find that evidence and logic is lacking, be even more skeptical about who benefits from them.
A Brief Primer on Health IT Problems
I have noted that numerous policy makers I've spoken with freely admit their knowledge of healthcare IT is zero, or limited to what they've seen and heard in the press (i.e., mainly marketing messages in disguise).
Since most of these officials have little time to study the issues about health IT in depth, I've created a zipped archive of four articles I consider key. The articles can serve as a primer on health IT problems:
The zipped file can be downloaded from here:
It is 2.7 Mb in length.
(A compilation of over fifty articles is at http://www.ischool.drexel.edu/faculty/ssilverstein/HITreadinglist.doc, for those with lots of time.)
-- SS
Since most of these officials have little time to study the issues about health IT in depth, I've created a zipped archive of four articles I consider key. The articles can serve as a primer on health IT problems:
1. Joint Commission Health IT Sentinel Events Alert, 2009.
2. FDA Internal Report on Adverse Events Involving Health IT. ("Not intended for public use" - but obtained by the press last year, presumably via FOIA), 2010.
3. ECRI Institute Top 10 Health Technology Hazards of 2011 - see hazard #5.
4. Hoffman/Podgurski, Case Western Reserve School of Law: E-HEALTH HAZARDS: PROVIDER LIABILITY AND ELECTRONIC HEALTH RECORD SYSTEMS - comprehensive article, one of a series, 2009.
The zipped file can be downloaded from here:
http://www.ischool.drexel.edu/faculty/ssilverstein/HIT_issues_Primer.zip
It is 2.7 Mb in length.
(A compilation of over fifty articles is at http://www.ischool.drexel.edu/faculty/ssilverstein/HITreadinglist.doc, for those with lots of time.)
-- SS
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