oracknows

Turning out the lights and moving on: Goodbye, old ScienceBlogs blog, hello new blog

oracknows — Tue, 31 Oct 2017 02:00:17 +0000

Turning out the lights and moving on: Goodbye, old ScienceBlogs blog, hello new blog

Today is the last day that ScienceBlogs will exist. Sometime today the site will go into read-only mode. A few days later, it will disappear completely from the Internet. It's a sad thing to contemplate after all these years. Whatever happened later, I will always be grateful for the start in blogging I got there.

But that's the past. The future is here:

respectfulinsolence.com

Some work remains to be done with the site, and I am not ready to produce new posts for it yet while these odds and ends remain to be taken care of. Due to a confluence of events in addition to still having to tweak the blog to my satisfaction, I am not sure if I will be able to manage to produce new material until Monday or Tuesday. (I'd rather that things be nailed down before I start writing again.) However, don't let that stop you from exploring, kicking the tires, commenting, etc. That'll help me figure out what the problems are and how things are working.

I will try to make sure that comments from the last couple of weeks transfer over, but I can't guarantee it given the tight timeline here. Either way, I don't recommend commenting here any more. it is also possible that some comments could get lost over at the new blog.

Of course, if something happens that so gets under my skin (or amuses me) before then, I might not be able to restrain myself, WordPress be damned.

oracknows Mon, 10/30/2017 - 22:00

A quick update on the migration to a new domain

oracknows — Mon, 23 Oct 2017 08:30:08 +0000

A quick update on the migration to a new domain

Here's a brief update on the move, announced last week.

Things are progressing, and most of my old material has been transferred to the new blog, which is located at respectfulinsolence.com. Of course, there are still some things to tweak and fix, which is why, given how insanely busy this week is going to be, given my impending trip to CSICon on Thursday afternoon, I've decided to hold off on writing new material for the new blog until sometime next week, probably November 1 or 2. I'm just gratified that there are so many of you who are still checking back and commenting. Please be patient.

This will officially mark the longest period of time in nearly 13 years that I haven't produced new material for Respectful Insolence. It feels a bit weird, and I must admit that there are things happening that make my keyboard fingers itch to comment on. I have thus far resisted. On the other hand, I should've taken a break more often before.

In any case, given that my traffic and Google juice are going to tank big time for a long time anyway, I might as well take my time and make sure everything's in good shape before opening the floodgates on the new blog. Also, before Friday I need to radically retool my integrative medicine talk for CSICon, both to fit it into a much shorter time period and to make it (hopefully) still interesting and worthwhile for anyone who was at QEDCon and saw my talk there. Oh, and let's not forget my real job, where I have to finish a final report on a grant that's due October 29. Damn real life interfering!

Yes, holding off until November 1 or 2 to begin Respectful Insolence, Mark III, seems a very good idea. Hang in there. It'll be just as good, if not better, than the current incarnation. Over time, I might even transfer material from Respectful Insolence, Mark I (my old Blogspot blog, which now exists only as an archive for the first 14 months or so of my blogging) over to the shiny new blog, so that all of Orac's Insolence can be found in one place. First things, first, though.

oracknows Mon, 10/23/2017 - 04:30

A change is gonna come. Respectful Insolence is moving.

oracknows — Mon, 16 Oct 2017 22:01:17 +0000

A change is gonna come. Respectful Insolence is moving.

Well, QEDCon is over, and this box of blinky lights is on its way back across the pond to its home in the US, having had an excellent time imbibing skepticism from its (mostly) British and European partners in skepticism.

Before I left, I made a somewhat cryptic remark about "major changes" to this blog coming up. Well, the cat's out of the bag, so to speak. Basically, Scienceblogs is shutting down at the end of the month. I still remain grateful for the opportunity Scienceblogs offered me. I wouldn't be as prominent as I am now without it. However, unfortunately, Scienceblogs has barely existed as an entity for a few years now. Unfortunately, Scienceblogs isn't just shutting down, it's going away completely.

As a result, I'm now in a frantic race to transfer all the old material to a new host. Sadly, I expect a lot of problems, because I have nearly 12 years worth of material to transfer, over 5,000 posts and 360,000 comments. Indeed, I've already encountered them. Let's just say that WordPress' export/import tools are not as...robust...as they could be.

Transferring the blog is going to be a big task, because it's necessary to break up the transfer into many small chunks, and then each import frequently requires multiple tries to get everything transferred. As a result, I've decided that I can't do this properly and still produce my usual level of quality output. So I'm going to stop blogging for however long it takes to transfer everything over. I expect that it will take at least a week. There will be an announcement here and on Twitter when I christen the shiny new blog with its first bit of new Insolence.

In the meantime, please do me a favor. If you run across the new blog (which isn't indexed on search engines yet while I make the transfer but it's also not too difficult to figure out the address), please don't comment. Until the transfer is complete, if I see any new comments on the new blog before I finish transferring all the material, I will delete them. Also note that if you're commenting now on a post published September 30 or early there's a chance your comment might not make the transition to the new blog.

I hope you all will all join me at the new blog when the transfer is complete. There are a number of advantages. One is that the Scienceblogs site is so...2011. The theme and design literally have not been updated since...around 2011. The new theme is much more responsive to mobile devices, adjusting itself nicely for desktop and mobile devices and a lot cleaner. Those of you who are inappropriately in comment moderation purgatory will be released.

I think you'll like it, and I think I'll like it.

oracknows Mon, 10/16/2017 - 18:01

And the box of blinky lights has arrived in Manchester for QEDCon

oracknows — Fri, 13 Oct 2017 07:00:13 +0000

And the box of blinky lights has arrived in Manchester for QEDCon

As you probably noticed, I didn't manage a post yesterday. Nor did I manage one today, other than this. That's because I was busy preparing for QEDCon, where I will be on a panel and giving a talk, and, of course, putting together my talk. As I write this, I'm horrendously jet lagged; so I probably couldn't write much that's coherent anyway. Consequently, there likely won't be any new posts until next week.

I will take a moment, however, to mention that there will be significant changes to this blog in the near future. It's a process that will likely take a couple of weeks, and I'll update you as I go along. I've told a handful of my readers what the change will be and why it's necessary, and others might have guessed. Fear not, though. I'll update you as I go along, and all will be clear soon. I've been doing this blog for nearly 13 years. It's such a part of my life that I can't imagine not doing it any more. So I will continue.

oracknows Fri, 10/13/2017 - 03:00

On the "integration" of quackery into the medical school curriculum

oracknows — Wed, 11 Oct 2017 07:20:33 +0000

On the "integration" of quackery into the medical school curriculum

QEDCon is fast approaching (indeed, I can't believe I have to leave for Manchester tomorrow night), and because my talk there will be about the phenomenon of "integrative medicine," I've been thinking a lot about it. As I put together my slides, I can't help but see my talk evolving to encompass both "integrative" medicine and what I like to refer to as quackademic medicine, but that's not surprising. The two phenomenon are related, and it's hard to determine which has a more pernicious effect on science in medicine.

One aspect of quackademic medicine that I probably don't write about as much as I should is the "integration" of quackery into the curricula of medical schools. Part of the reason for that, I suspect, is that I am fortunate enough to be faculty at a medical school and cancer center that remain relatively untouched by the pseudoscience of integrative medicine. True, our medical school does have at least one credulous lecture about "complementary and alternative medicine" (CAM) that the medical students have to imbibe, but it really is pretty close to the bare minimum required by the accrediting agencies. Oh, yes. Proponents of integrative medicine have been so successful that one requirement for accreditation by the Liaison Committee on Medical Education (LCME) is that there be adequate instruction about CAM. Actually, that's not quite true. Among the educational objectives in the LCME requirements is ED-10: "The curriculum of a medical education program must include behavioral and socioeconomic subjects in addition to basic science and clinical disciplines." This is where CAM and integrative medicine are slipped in. That's because the Academic Consortium for Integrative Medicine and Health successfully lobbied the LCME to include CAM in its list of topics addressed in the LCME Medical Education Database relative to accreditation standard ED-10. Unfortunately, how that is done in practice is often in the form of entirely credulous teaching of CAM.

Last month, when I wrote about the $200 million donation to the University of California, Irvine (UCI) by the billionaire couple Susan and Henry Samueli to create a college of health sciences that will encompass several UCI schools, including its school of medicine and nursing school, dedicated to "integrating" quackery at all levels into medicine thusly:

The Samuelis’ gift will provide $50 million toward construction of a facility to house the college and $5 million for state-of-the-art technology and labs – forming the foundation of a national showcase for integrative health. It also earmarks $145 million to create an endowment for:

Up to 15 faculty chairs across the medicine, nursing, pharmacy and population health disciplines for senior, midcareer and junior faculty with expertise in integrative health

Integrative health training and mentoring for interested medical school students

Scholarships and fellowships for undergraduate and graduate students planning careers in related fields

Innovative curricular development and campuswide interdisciplinary research projects

Ongoing clinical services, research and education in the Susan Samueli Integrative Health Institute, including investigations of nonconventional interventions as part of medical treatment and educating medical and lay communities about benefits and risks associated with new healthcare approaches

What I didn't talk about so much was number 3: "innovative curricular development." That's CAM-speak for teaching CAM alongside real medicine as though homeopathy has scientific validity. This brings us to an article by noted cheerleader for "integrative medicine" Glenn Sabin, Integrative health's place in the medical school curriculum. If you want to know where Sabin's coming from, consider my previous discussions related to his promotion of alternative medicine, such as his "history" of the integration of quackery with medicine and his advocacy for anecdotal evidence disguised as "N-of-1 trials" over clinical trials in determining if various alternative medicines "work." He also first got my attention for openly admitting that integrative medicine is a brand, not a specialty. Also consider this paragraph from his latest:

My colleague, John Weeks, wrote a terrific response in Huffington Post to the media’s shameful coverage of the visionary and game-changing Samueli gift to UCI. He cogently supports his position with actual research, facts, and developments that illustrate just how out-of-touch these dwindling skeptics are—and how a few media outlets took the bait that led them down a narrow-minded narrative centering on one controversial therapy: homeopathy.

For me, though, the back-and-forth with the cynics is not worth the expended energy. This is not just about acupuncture or chiropractic or massage or dietary supplements. It’s much bigger.

The Samueli gift is about the future of health, led by the doctors of tomorrow, like my nephew, Max, who is in his first year of medical school at George Washington University.

Homeopathy is not "controversial." It is rank pseudoscience. This is not even in dispute. Just look at the way UCI started furiously scrubbing its websites of references to homeopathy as soon as critics started looking at the Samuelis' gift in detail. Clearly, the administration was embarrassed. I also note that one earlier gift agreement between the Samuelis to UCI explicitly mentioned that it was to be used to promote research into homeopathy, among other pseudoscientific modalities and that until recently UCI advertised the services of a naturopath and homeopath on its website. Even proponents of integrating quackery into medicine are embarrassed by homeopathy.

When discussing the "integration" of quackery into medical school, I like to discuss another "George" university namely Georgetown. In many ways, it was a "trailblazer" in "integrating" quackery into medicine. I recounted its history just a couple of years ago, citing a 2003 Georgetown brochure:

One of the reasons CAM is usually offered as an elective is that there’s just no time or room in U.S. medical schools to fit in one more massive subject,” says Michael Lumpkin, Ph.D., professor and chair of the department of physiology and biophysics at Georgetown. “When the course is an elective, a self-selected group – maybe 10 or 20 students in a class of 180 medical students – will take it,” Lumpkin says. “What we’ve tried at Georgetown is rather than create all new courses, we take relevant CAM issues and modalities and weave them seamlessly into existing courses.

The “seamless” weaving of CAM into existing classes includes, for instance, a presentation by an acupuncturist on the “anatomy of acupuncture” in the gross anatomy course for first-year students. The same lecturer explores acupuncture’s application in pain relief in the neuroscience course…

Haramati and Lumpkin say Georgetown’s program is distinct from CAM initiatives in other medical schools in two ways: The school is integrating CAM education into existing course work across all four years of each student’s medical education, and the initiative includes a mind-body class to help students use techniques to manage their own health and improve self-care.

Yes, fourteen years ago, Georgetown was "integrating" pseudoscience into its medical school curriculum at every level, starting from day one. Twelve years later, it was celebrating pseudoscience on the cover of the medical school's magazine. That's not all, though. Reflexology is taught as fact, along with prescientific medical systems, such as traditional Chinese medicine (TCM), "energy healing" like reiki and therapeutic touch, and pretty much every "integrative" quackery you can think of. In 2007, Georgetown partnered with the naturopathy school Bastyr University to train the next generation of integrative medicine practitioners.

This is the sort of future of medicine that Weeks and Sabin so strongly desire.

It's also not as though George Washington University isn't itself a bastion of quackademic medicine. Three years ago, I wrote about all the quackery advertised on its website. GWCIM's list of services includes acupuncture (of course!), chiropractic, craniosacral therapy, infrared light therapies, glutathione infusions, Myers’ Cocktail, naturopathy (again, of course!), reiki, intravenous high dose vitamin C, and genetic profile results that include “customized interpretation of 23andme.com genetic profile results with specific accent on methylation and detoxification profiles.” It’s a truly horrifying website to contemplate, given how little of it has any resemblance to science-based medicine and how much of it includes outright quackery like reiki. In addition, its website’s descriptions of various alternative medicine modalities are depressingly and similarly credulous. Acupuncture is described as being used for “for treatment of respiratory, digestive, urinary and reproductive systems, as well as the disorders of muscle tone, hormone production, circulation, and allergic responses” plus “pain relief, gynecological conditions and symptoms, insomnia, anxiety, and to enhance wellness.” Naturopathy is described as a “comprehensive approach to health and healing that combines modern scientific knowledge with traditional and natural forms of medicine,” with naturopaths addressing “the mental, emotional and physical aspects of an individual, and aim to treat the root causes as well as the symptoms of illness.” According to GWCIM, naturopaths are “trained as primary care doctors at accredited four-year naturopathic medical schools.”

No. They. Aren't.

I also can't help but note that John Weeks' article was really nasty broadside against critics of the Samuelis' gift to UCI in which he accused them of having "blood on their hands." Apparently, Sabin approves of such rhetoric, as long as it's directed against his opponents.

Sabin's article is yet another example of how "integrative medicine" rebrands science-based modalities, such as nutrition, exercise, and lifestyle modification as somehow "alternative" or "integrative" and then uses them as the vehicle in which quackery is also "integrated" into medicine, while trying to dismiss anyone who points out the pseudoscience as the "old guard—the few out-of-touch, aging critics pushing back." (I note that Sabin and Weeks aren't exactly spring chickens themselves.) Naturally, he tries to push back against the critics' narrative:

These same integrative health and medicine naysayers essentially conflate quackery—which ought to be called out and confronted—with the larger, progressive, and impactful, integrative health and medicine movement.

Critics also purport that nutrition, physical activity, and stress reduction are already consistently applied (or taught) clinically—that it’s already ‘part of medicine’. These few critics are wrong. Their view is incorrect. Their statements are patently false. We know this because, if these truly preventative measures were applied—if this was remotely the case—our healthcare delivery system would be consistently delivering ‘health care’, not ‘chronic disease care’.

Proponents of integrative medicine always try to sweep all the quackery their specialty embraces under the rug. Pay no attention to that quackery behind the curtain, they say. We're all about nutrition, lifestyle, and stress reduction. They somehow never manage to address the question: Why is quackery so associated with integrative medicine? If integrative medicine really were about "nutrition, lifestyle, and stress reduction" and nothing else, the quackery would be unnecessary. Homeopathy, naturopathy, acupuncture, "energy healing," functional medicine, bogus allergy testing, and more forms of pseudoscience and quackery than I can list here (but have discussed over the years on this very blog) would not find such a comfortable home in "integrative medicine." That they do fit so nicely in "integrative medicine" is by design, not accident.

Consider this. Let's, for the sake of argument, concede that Sabin has a point. Perhaps nutrition, physical activity, and stress reduction are not sufficiently consistently applied in clinical medicine. If that is indeed the case, the answer is to develop strategies to change this shortcoming in medicine. Those strategies, assuming they're science based (as they should be), will not involve embracing pseudoscience and quackery. Sabin and Weeks go on and on and on about promoting the "nutrition, physical activity, and stress reduction" aspect of medicine, but fail to explain why a separate specialty is needed to emphasize these health promotion activities more. That's because they can't. The entire unspoken rationale that they cannot admit is that "nutrition, physical activity, and stress reduction" function, in essence, as a Trojan horse for hardcore quackery. Integrative medicine shows up at the gates of academic medicine looking like ""nutrition, physical activity, and stress reduction," but once the horse is pulled into the ivory tower of academia, out jumps the real quackery, like naturopathy, homeopathy, acupuncture, functional medicine, and the like.

Also unspoken is that the reason integrative medicine proponents want so badly to insinuate their specialty and thinking into medical school is because they want "nutrition, physical activity, and stress reduction" forever linked with the quackery that they also champion. At schools like GWU and Georgetown, it's working, too. I fear, however, that UCI will soon far surpass both GWU and Georgetown as bastions of quackademic medicine.

oracknows Wed, 10/11/2017 - 03:20

Another antivaccine paper bites the dust

oracknows — Tue, 10 Oct 2017 01:15:24 +0000

Another antivaccine paper bites the dust

I've written on quite a few occasions about a pair of scientists beloved by the antivaccine movement. I'm referring, of course, to Christopher Shaw and Lucija Tomljenovic. Whether it is their publishing dubious "evidence" that HPV vaccines cause premature ovarian failure or even death or demonizing aluminum as a vaccine adjuvant, Shaw and Tomljenovic publish nothing but antivaccine pseudoscience that antivaxers love to cite whenever they dump some turd of a study on the medical literature.

Just last month, they dumped their latest turd of a study, in which they basically tortured mice in the name of pseudoscience. Later, after I wrote my first analysis of the study in which I described how poorly designed and executed the experiments were, I discovered that there's more than just bad science there. There's possible fraud, as circulating on PubPeer are reports of image manipulation that are quite convincing. At the time this rather obvious image manipulation was being discussed, so, too, was the possibility of retraction. After all, if there's one thing that merits pretty much an automatic retraction in science, it's manipulation of images presented as data in a scientific paper.

Not surprisingly, then, yesterday I learned from Retraction Watch that Shaw and Tomljenovic's latest paper will be retracted as well. The editor of the Journal of Inorganic Biochemistry announced that the journal will be retracted:

The journal’s editor, John Dawson of the University of South Carolina, told Retraction Watch:

The paper by Shaw and co-workers is being retracted jointly by the authors and the editor.

He noted there will be a “statement accompanying the retraction of the paper.”

Shaw told us that his lab began investigating the issues raised on PubPeer “within a day” and reported its findings to both UBC and the journal soon after. He said:

Our own analysis showed some figures had been altered. We requested a retraction because we could not understand how that had happened. We felt the data had been compromised.

Shaw said that the problems mostly lie with data showing no change in gene or protein expression levels after aluminum injections — but also with some data showing changes in expression, which the paper attributed to the injections.

Next up, Shaw tries to pass the buck:

Shaw said that first author Dan Li, a former postdoc who performed the molecular biology and gene expression analysis for the study, has agreed to the retraction but not yet offered an official explanation about the data. Shaw told us:

She denied that anything had been manipulated, or that anything was amiss.

He added that when Li left the lab in 2015, she took the original data with her:

UBC policy is that original data never leave the lab. We’ve asked for them to be returned to us.

Shaw said he thinks the core data are “probably correct,” but said he plans to have the experiments re-done:

It is what it is. We’ve done everything we can on our end. We’re still having conversations with Li on where the data are and how we get them back. That’s as much as we can do at this point.

I suppose that it's possible that Shaw was duped by a postdoctoral fellow in his laboratory. When you're the head of a lab and the principal investigator of a study, you tend to come to trust those working for you. You don't want to think that one of them might be committing scientific fraud by manipulating images. On the other hand, as PI, one has to be on guard for this very thing. The PI is basically the captain of the ship, and the buck stops at his desk, and whatever other cliche you want to invoke to say that he is in charge and responsible for the integrity of the data produced by his lab.

The kindest possible interpretation is that Christopher Shaw runs a loose ship, so loose that he didn't notice that many of the bands on the images of his DNA gels and the autoradiographs of his Western blots were duplicated, flipped, and otherwise manipulated. Certainly, letting the raw data and raw images out of the lab is not good lab practice, particularly in this day and age, when pretty much all images of gels and Western blots are recorded digitally. In my lab, for instance, there is a lab shared drive, and every single image generated is stored there, so that original images used to make figures can always be recovered. PRanoid PI that I am, I even periodically copy the whole shared drive to my own computer, which in turn is regularly backed up. Key figures are preserved on cloud drives.

The worst possible interpretation is that Shaw either knew about the image manipulation (or even ordered it) or that he put so much pressure on his postdoc to produce results that she felt that she had to falsify figures to produce what he wanted. Of course, I wonder about Shaw's practices. For instance, in my discussion of the image manipulation, I noted that Shaw and Tomljenovic have at minimum engaged in self-plagiarism, recycling figures from a 2014 review article into which they dumped a little original data in their soon-to-be retracted paper. So, in terms of commonly accepted practices, we already know Shaw's rather...unconcerned.

Then, of course, there's Shaw and Tomljenovic's history. Back in 2015, they published a paper purporting to show that aluminum adjuvants in Gardasil caused behavioral abnormalities in young female mice that was retracted for this reason:

This article has been withdrawn at the request of the Editor-in-Chief due to serious concerns regarding the scientific soundness of the article. Review by the Editor-in-Chief and evaluation by outside experts, confirmed that the methodology is seriously flawed, and the claims that the article makes are unjustified. As an international peer-reviewed journal we believe it is our duty to withdraw the article from further circulation, and to notify the community of this issue.

Why is it that the University of British Columbia and its Department of Ophthalmology (which is the department where Shaw and Tomljenovic are based) put up with crap like this? Shaw must have tenure or pictures of the Dean having an affair. I can't think of any other reasons why he isn't long gone.

Ultimately the article was republished in a form that was nearly word-for-word identical version in an inferior journal. Such is the fate of antivaccine pseudoscience. It always comes back. That's why I liken it to zombies, Jason Voorhees, Michael Myers, Freddy Krueger, Chucky, or any other monsters that "die" at the end of one movie, only to inevitably reappear in a new sequel over and over and over again.

I have little doubt that Shaw and Tomljenovic's soon-to-be retracted paper will reappear somewhere else within a few months. It's what antivaccine scientists publishing dubious or even fraudulent research to promote the long discredited idea that vaccines cause autism do. Their pseudoscience never dies. It just keeps being recycled like the sequel to a 1980s slasher flick.

oracknows Mon, 10/09/2017 - 21:15

A conversation with a Rigvir flack

oracknows — Mon, 09 Oct 2017 01:36:38 +0000

A conversation with a Rigvir flack

Over the last two Mondays, I've been writing about an unproven cancer therapy that I hadn't really heard much about before. The cancer treatment is called Rigvir; it is manufactured in Latvia and marketed primarily through a Latvian entity called the International Virotherapy Center (IVC).

To recap, Rigvir is an unmodified Echovirus, specifically ECHO-7, that, according to the IVC, seeks out cancer cells, replicates in them, and thus lyses the cancer cells (causes their membranes to break, spilling out the cancer cells contents, thus killing the cell), hence the term "oncolytic virus."

Somehow, mysteriously Rigvir was approved by the Latvian equivalent of the FDA in 2004 for the treatment of malignant melanoma despite what appears to have been grossly inadequate supporting evidence and then even more mysteriously placed on the Latvian Health Ministry's list of reimbursable medications in 2011. I suspect that the reason that I didn't look into Rigvir earlier was probably because its use had been primarily restricted to Latvia, Georgia, and Armenia. Also, there was the language barrier.

Nearly everything available on the web about Rigvir is in Latvian, a situation that has only recently begun to change.

It was Antonio Jimenez and Ty Bollinger who plucked Rigvir from obscurity. Dr. Jimenez runs the Hope4Cancer Institute clinics in Baja and Cancun, Mexico, and, for whatever reason (probably profit), these clinics started offering Rigvir relatively recently. Then, Jimenez, who's clearly worked with Bollinger in the past, must have turned Bollinger on to Rigvir, and Bollinger included it in a long segment of Episode 3 of his The Truth About Cancer (TTAC) propaganda series of videos. It was this connection and the deceptive use of patient testimonials by both Bollinger and the International Virotherapy Center to sell Rigvir that formed the basis of my second post on Rigvir last week.

As you might imagine, apparently the management of the IVC was not happy about my posts. In fact, so unhappy was the management of the IVC that within 15 hours of my first post about Rigvir going live I got an e-mail from someone named Lelde Lapa, whose title was listed as Assistant of Business Development Department at the IVC, protesting and attempting to refute my post. As I noted before, I was amazed at how fast I received such a long e-mail after publishing my post. Clearly the IVC has many Google Alerts set for Rigvir and its name and was fast to act.

What followed was an exchange that currently stands at five e-mails, three from Ms. Lapa, with two responses from me, with Ms. Lapa's tone (if it indeed was only one person writing these) becoming more strident as the exchange went on. Because these e-mails are a great insight into the thinking (such as it is) at the IVC, I decided that a most excellent way to conclude my series on Rigvir as a trilogy would be to annotate and publish these e-mails, and then to compose a final response to Ms. Lapa's third email, at the end of which Ms. Lapa told me that I didn't need to respond. Clearly she don't know me vewy well, do she?

So let's begin. Remember that English is not Ms. Lapa's native language; so be kind. I wasn't kind, but not because of any difficulties Ms. Lapa might have had with English.

Rigvir strikes back, round 1

So on the afternoon after my first post about Rigvir went live, I was greeted by this in my e-mail in box:

From: Lelde Lapa < [REDACTED]@virotherapy.eu> To: [redacted] Subject: Blog about RIGVIR Date: Tue, 19 Sep 2017 00:54:53 +0300 Organization: RIGVIR Development department Orac: Yesterday we encountered one of your blogs (https://sciencebasedmedicine.org/rigvir-another-unproven-and-highly-dub…) Due to the fact that this blog is now widely spread by non-professionals with the title – independent conclusion from international expert, we believe we have the rights to inform you that you are used now as a tool in competition wars. Which we believe was never your intention. The medicine RIGVIR has a clinical experience for more than 50 years and it is registered for melanoma for more than 13 years and before the era of modern trials and most of the evidences is not published. Doctors and clinics in Latvia use this medicine for majority of melanoma patients in Latvia for many years. In Latvia medicine is prescribed only in national clinics and by certified doctors and they have also other alternatives, so probably they know what they do. 2 years ago we started EMA (centralised EU) commercialisation process and even obtained EU commission support from Horizon2020 grant, we also obtained EMA regulatory advice. There is no doubts about the efficacy and safety of the medicine, however we acknowledge that we miss modern trials for centralised registration and we are working on them. This was never a secret to discover. But year ago a group of very active, mostly anonymous people appeared that started to attack us, our cooperation partners, even EU commission, spreading bias data or even lies. They are very aggressive. Part of the sources they use does not exists, part of materials are generated by them self and republished in different sources mostly social networks, then in blogs and then cross-referenced. Part of material is made as compilation of different phrases and translated in English with certain pseudo professionals on them (By the way two such persons appears also in your blog, these persons however has no proper educations, has never been involved in medicine or science). Moreover at the spring anonymous letter (your blog also indicated it ) appeared. It was signed by few professional organisations of which only 2 are related to oncology and in fact were represented by the same people, this letter contains ~80 lies and tendentious distortion of information. Unfortunately there is no author on the horizon to be responsible for aspersion, but there have been cases when TV and portals have withdrawn similar articles and information about us already. Mostly your blog analyses openly available data, but partially it contains false information. It contains also comments of pseudo professionals or anti-PR specialists but the producer of RIGVIR was never approached for clarification or comments. Which is sad especially, referring to the statement from the blog: “Somehow I doubt Rigvir will make it that far. At least, I sincerely hope that it doesn’t….” We believe that also blogs should be objective and respectable professors should use only proven data and also verified sources. So please consider to here also our position and obtain more information about virotherapy with RIGVIR, like clinical trial data and post-registration experience. We do provide special trainings for doctors and medical scientists. I hope you are interested, Looking forward for your replay. Best Regards, Lelde Lapa Assistant of Business Development Department www.virotherapy.eu

Of course, I had no idea who this Lelde Lapa was. I couldn't really find anything about her. A Google search of the IVC website for her name didn't reveal anything. For my purposes, it doesn't really matter, but I did find it odd. I can't help but note here that, although I do not claim to be completely objective, my bias is rather well known: I favor science as the basis of determining which medical treatments do and do not work. I make no bones about that. Moreover, I couldn't help but immediately note that it's pretty hard to use "only proven data" when there is so little in the way of proven data upon which to evaluate Rigvir. That was, in fact, my key problem with the drug, that it is unproven and being marketed without sufficient scientific and clinical evidence that it does what is claimed for it. Here was my response, sent later that evening:

Dear Ms. Lapa: The Virotherapy Institute must be very on top of its social media to have noticed my post and composed such a lengthy e-mail to me within 15 hours or so after my post went live. If you have any specific examples of errors in my post, feel free to point them out. What I see in your letter is not that; rather, it is spin, as nothing you wrote actually casts into doubt any facts included in my post or in any of my interpretations of those facts. Yes, I used publicly available information because that’s what many bloggers do when they compose posts. Besides, I was interested in what I view as the irresponsible marketing of Rigvir for more than just melanoma, and there is plenty of that to be found on the Internet and social media. The two videos on your website that I discussed fall into that category, without a doubt. In your e-mail, you state that there are "no doubts about the efficacy and safety of the medicine,” but there are doubts—a lot of doubts—so much so that my jaw dropped when I read that. The reason is simple. You yourself said it: “...we miss modern trials for centralised registration.” Basically, you don’t have anything resembling the level of scientific evidence required before we accept any drug as effective and safe. You have no randomized double-blind clinical trials. All you have are a handful of case reports, a couple of very poorly done retrospective studies, and ancient evidence from decades ago that cannot be inspected and assessed for scientific rigor. In my country, our Food and Drug Administration would laugh at such data. If you’re making health claims for your product, particularly the glowing claims made about Rigvir’s anticancer activity, then all that matters to me is whether there is solid evidence to back up those claims published in the peer-reviewed medical literature as indexed on PubMed. Of course, this evidence must be in the form of papers reporting improved recurrence-free and overall survival in well-designed, randomized double blind clinical trials of your product for every cancer for which a claim of efficacy has been made. I do not care about unpublished data that I cannot examine myself. I do not care about claims. I do not care about “registration,” as clearly the registration process in Latvia at the time Rigvir was registered left a lot to be desired. I do not care about pilot grants to start to work on approval by the EU. None of that matters when evaluating a therapy if there is no good clinical trial evidence supporting its efficacy and safety. Unless you can provide me with those data, I have no choice but to find your complaints about my article to be without merit. If Rigvir has been proven safe and effective and isn’t quackery, then why are you selling it to quack clinics in Mexico and Germany? I’m serious. Hope4Cancer, for instance, is a notorious quack cancer clinic that attracts Americans with cancer. This is not in dispute and can be verified by simply reading the Hope4Cancer website and examining the treatments it offers cancer patients. Also, if Rigvir has been proven safe and effective and isn’t quackery, then why was it featured on Ty Bollinger’s “The Truth About Cancer” video series and, more importantly, why is the administration of the International Virology Center proud of being featured in his videos? Bollinger is a notorious promoter of cancer quackery. (I can provide many examples of him promoting dubious, unproven, and quack treatments for cancer.) No reputable company selling a cancer treatment scientifically proven to be effective and safe would ever want to be associated in any way with the likes of Hope4Cancer or Ty Bollinger, because it would tarnish its brand and bring it into disrepute. In actuality, your response makes me more confident than I was originally that I was correct in my assessment. Your paranoia, for instance, is makes me very suspicious. You rail against “anonymous people” attacking Rigvir and the Virotherapy Center, but isn’t it true that the complaints to the Latvian Health Ministry came from the two main oncology professional associations in Latvia? That’s hardly “anonymous.” They are respected professional medical societies! I also have seen quite a few criticisms of Rigvir on blogs and have been able to identify everyone making the criticisms so far. Perhaps you meant The Mad Virologist, but he isn’t really anonymous either. His name is in his Facebook profile, which I found in two minutes. Complaints about “anonymous” people out to disparage a product always make me think a company has something to hide. Finally, I understand that you and Latvia are proud of Prof. Muceniece’s accomplishments, but ask yourself this: If she were alive today, would she want her name associated with selling her discovery before it’s actually scientifically demonstrated to prolong the lives of cancer patients or cure specific cancers? Orac

In actuality, I had no idea whether Prof. Muceniece would care what the IVC is doing. I just wanted to see if there was any sense of shame over what the IVC was doing with her invention.

Rigvir strikes back, round 2

A couple of days later, I received this. For reference, the blog by Eduards Ritums was discussed in my first post and used in part as a basis for some of my criticisms. In any case, note the somewhat paranoid tone. I also showed my e-mails to a skeptic from Latvia who has been active investigating Rigvir, who thought that the style changed enough that it might have been written by someone else. I don't know for sure if that is the case (you can judge for yourself), but I do know that the fallacies and dubious arguments flow freely and with paranoia:

From: Lelde Lapa < [REDACTED]@virotherapy.eu> To: '[REDACTED] Subject: RE: Blog about RIGVIR Date: Thu, 21 Sep 2017 10:03:42 +0300 Organization: RIGVIR Development department Dear Orac As we indicated in our last email your blog now is spread widely in Latvia as a proof that our medicine is not effective. Was it a goal of your blog? We got impression that the blog is a part of wider campaign that is currently in place in Latvia and therefore we just wanted to warn you ASAP and protect your reputation by providing more information if you are ready to hear it. Part of your blog is based on the article that is published by author E.Ritums initially in very specific marketing magazine for Pharmacies. This magazine is published by Medicine Information Centre (http://mic.lv/materia-medica/ ) that is not registered in the register of mass media and even provide marketing services (http://mic.lv/materia-medica/). In addition the content of this magazine (according to law in Latvia) is considered to be specialised publication and may not have public access. The author however (based on google search) is young graduate from faculty of Chemistry that in addition to this particular article has published few (~3) more small articles and hardly is respectable journalist. Particular publication consists of number of fact errors and doubtful allegations and there is no respectable or proven sources, books or reviewed publications indicated as reference. Moreover former manager (for 12 years) of the same publisher and magazine Inara Rubene ( https://www.linkedin.com/in/inara-rubene/) is presented as independent expert here. The biggest issue is, however, the fact that this article later, bypassing limited access info (according to law) to specialists, was translated (with inconsistencies) and spread widely with help of very small, non registered NGO – Skeptiskā Biedrība (https://www.lursoft.lv/lapsaext?act=URCP&ref=LurTop&regcode=&task=searc…), that operates web site – www.skepticisms.lv. Do you consider this as trustworthy source to build part of your story on? Please note that official page of the product RIGVIR is rigvir.com and there is no marketing at all. Page virotherapy.eu is mostly dedicated to therapy not medicine – there are news, testimonials and trainings. It is not a clinic or pharmacy to speak about marketing. Should we hide testimonials, if there are such? In Latvia there are very strict regulations for marketing of pharmaceuticals and there is no official judgment from Latvian Health Inspection about as you say “irresponsible marketing”. Moreover the only one claim from Latvian Health Inspection, that initially was stated so, is already changed clearly stating that we cannot be responsible for third party activities. As you know the clinical studies are done mostly for official approval of medicine and according to Bloomberg at least one third of studies are never published. So if you are clearly stating that you don’t care about unpublished data, then please adjust title of your blog to something like “Analysis of published data of RIGVIR”. Because ignoring unpublished clinical trials for more than 30 years, you simply don’t have all the facts to loudly state that our medicine is not effective or it should be avoided. Let us clarify that medicine RIGVIR is registered in Latvia in 2004 for Melanoma, before the era of modern requirements for trials, but based on clinical trials during 30 years period in which ~700 patients was treated with the medicine RIGVIR (there is also registration in Georgia and Armenia). The medicine is used as conventional therapy in Latvian, Georgian and Armenian clinics. In addition to that, patients from all over the world are coming to Latvia or sometimes are sending relatives or trust-persons to Latvia to buy this medicine in case traditional therapies have not succeeded or are not well tolerated. Yes we do train medical doctors from all over the world and probably their patients also have acquired medicine from Latvia. We know that the medicine is effective, we have seen it working on many thousand cases and we clearly know that it has no side effects. So knowing that, should we refuse to help patients of any Doctor? We are not company that is developing innovative solution and according to the heritage of the founder prof. A.Muceniece the medicine should be available to as many patients as possible. We are not refusing the knowledge and information to any official doctor, official clinic or patient groups. So we don’t see any problem also from appearing in The Truth About Cancer series. Most of our critics and also yours complains are catch-22 logic – “give us evidences before you use it -> new evidences requires investments -> to provide investments we need to use medicine –> to use medicine we need to be commercialised -> but with the existing evidences you doubt us to be commercialised …” As if only rich pharmaceutical or biotechnological companies may work in the field… You are stating that you don’t care about existing registration, but unfortunately your analysis is used to doubt the registration. Which is off course strange, because nowhere in the world rules and regulations (in our case standards for clinical trials) are used with backward date. Yes for new registrations - we know the rules – we will provide proper RCT data, but as for now, please respect that the medicine is prescription medicine that is prescribed only in national clinics and by certified doctors for last 13 years. They have alternatives and even reimbursed ones. So obviously these doctors have deeper knowledge about the therapy with RIGVIR, than just analysis of published data, since it is used for more than 70% of Melanoma patients in Latvia. We suggest you to learn about this therapy and try it yourself for your patients (that follows entrance criteria) as well. In such case and with your commitment to make case report and publish it, we would provide all the necessary assistance and medicine free of charge. Best Regards, Lelde

Gee, Ms. Lapa makes the observation that my blog post has been circulated far and wide in Latvia as evidence that Rigvir doesn't work as though that were a bad thing! In actuality I can't help but feel a bit of a warm and fuzzy feeling in the pit of my cold, black heart that my post has actually been circulated far and wide in Latvia. Those behind IVC will probably take this as evidence that I'm out to get them, but I'm not. I'm out to protect cancer patients. If the IVC had the goods, as far as evidence, the easiest thing for its management to do would have been to publish it or somehow show it to me and other skeptics who are concerned that Rigvir is cancer quackery. We can be persuaded, but it takes evidence. Finally, notice that last part, in which "Ms. Lapa" tries to co-opt me, thinking that if I were to try Rigvir I would conclude that it works. I've noticed this pattern before, and where I've noticed before it isn't flattering to Rigvir or the IVC. You see, I've discovered that when it comes to cancer quackery or unproven cancer treatments I seem to have special cachet because I am a cancer surgeon and researcher. Thus, from time to time, cancer quacks try to convince me to try the treatment they are selling on my own patients. In my response, I decided to stomp down hard on this offer after giving a bit of a lecture. See what you think:

Ms, Lapa, Although I appreciate your concern about my reputation, I think I’m probably the best judge of what will or will not damage it. In other words, I’ll take my chances. Regarding Eduards Ritums’ article, which I did cite extensively, I tend to judge an article and its main arguments far more by quality in terms of evidence, science, and reason than by who wrote it. Even though the article I read was an English language translation, Mr. Ritums’ central thesis and arguments nonetheless came across as very sound. It doesn’t matter if he’s young and early in his career and thus hasn’t published very many articles yet. In other words, who cares if Mr. Ritums published his article in a pharmacy magazine and is a new journalist? I certainly don’t. As for whether the magazine is “registered” or not, as far as I’m concerned that is a matter of your country’s specific laws and ways of doing things. It means very little to me as an American reading a translation of the article. In fact, it wouldn’t matter to me if Mr. Ritums wrote for an unregistered blog under a pseudonym if his arguments, science, and evidence were sound. Certainly, you have not demonstrated that they are not sound; you state that there are a “number of fact errors and doubtful allegations,” but, oddly enough, you have not actually specified the errors of fact or “doubtful allegations,” much less used evidence and science to show that they are factual errors or doubtful allegations. You have instead engaged in nothing but ad hominem, which is a logical fallacy. To convince me, you’re going to have to get a lot more specific and provide the evidence to back up your criticisms, something you have not yet done after two long e-mails. I find this very telling. As for your claim that official Rigvir website is not about marketing, I beg to differ. The whole website is clearly all about marketing, as all pharmaceutical company websites are. Indeed, it looks just like any other pharmaceutical company webpage promoting its products, complete with slick videos, like the one on this page. Basically, your website looks like any of a number of websites pharmaceutical companies maintain for individual products, like Herceptin, OncoTypeDX, or various new drugs. It’s not quite as slick, but it is very similar in appearance and content. True, it doesn’t contain patient testimonials, but that doesn’t make it any less a marketing website. Regarding the testimonials on the Virotherapy Center website, as a surgical oncologist, I find them quite misleading. Insufficient information is provided to allow me to judge whether Rigvir might have had an effect, and one in particular is definitely not evidence that Rigvir had a positive effect. Again, when I accused you of irresponsible marketing, I did it from my perspective as a cancer surgeon and researcher. Again, I really don’t care what Latvian law says with respect to marketing pharmaceuticals. Clearly, from my perspective, Latvian law is far too lax if it allows you to market Rigvir. You say that Rigvir was registered in 2004, “before the era of modern requirements for trials.” I hate to tell you this, but the basic standards for modern clinical trials were codified decades before that. In the US, it was 55 years ago in 1962 when the Kefauver-Harris Amendment to the law creating the FDA mandated that the FDA to require rigorous clinical trial evidence of efficacy and safety before it approves a drug for marketing. Are you honestly telling me that 42 years after that Latvia still didn’t require such evidence before approving a drug? If true, I find that shocking. Be that as it may, Latvia’s lax drug regulation 13 years ago is not an argument in support of the efficacy and safety of Rigvir even for melanoma, much less other cancers. Certainly, it doesn’t excuse you from selling the drug to a quack clinic in Mexico. And, make no mistake, Hope4Cancer is a quack cancer clinic, as I have documented elsewhere. (It even offers coffee enemas.) I’d suggest that, if you really want Rigvir to be accepted outside of Latvia, Georgia, and Armenia, selling it to a quack clinic to market to patients it is not a winning strategy. It will taint Rigvir with the stench of quackery. I’d highly suggest that you sever all ties with these clinics immediately, but I suspect that suggestion will fall on deaf ears. You say over and over that you “know” that Rigvir is effective. The fact is that you do not, at least not based on science and clinical trials, which is how doctors are supposed to know which drugs work and which do not. You claim that I ignored 30 years worth of clinical trials. Whose fault is that? You haven’t published them in a form that can be critically examined. If you had, I would have critically examined them. You wouldn’t even have to translate them into English. I’m sure I could find someone to translate the data for me if you were to publish all this data. Why don’t you? No, I will not change the title of my post. It is accurate, as far as I am concerned. I stand by my opinions and conclusions, and, yes, I still strongly believe that you should stop marketing Rigvir until such a time as clinical trials show it to be safe and effective. Certainly it should not be used for any cancer other than melanoma, and even for melanoma I don’t think you’ve shown sufficient evidence that it works to justify marketing it. Again, I say this because you can’t show me any decent scientific or clinical trial evidence to change my mind. Again, why is that? Does this evidence actually exist, or does it actually show Rigvir has such miraculous effects against melanoma? I suspect that it either does not exist or is not nearly as impressive as you claim. Indeed, there is a contradiction here. You say that 70% of melanoma patients in Latvia since 2004 have been treated with Rigvir. Why is it, then, that you could only find 52 melanoma patients treated with Rigvir for your 2015 Melanoma Research paper? Finally, although I am intrigued by your offer to provide Rigvir for free for me to try on my patients, unfortunately I don’t see how I can do it. Let me explain to you how we do things in the US. Doctors here can’t just go around administering unapproved drugs willy-nilly to patients if we feel like it. Were I to administer Rigvir to patients without proper approvals, I would quickly find myself in deep legal trouble—and rightly so! Were I to want to administer Rigvir to patients, it would have to be in the form of a clinical trial. I would first have to submit an Investigational New Drug (IND) application to the FDA, because Rigvir is not approved in the US. The FDA would then have to approve it. Next, I would have to write a protocol for a clinical trial. Let’s say I chose to do a phase I clinical trial, which would not require randomization. That application would have to be approved by the FDA and approved by my institution, specifically my cancer center's Protocol Review and Monitoring Committee and my university's Institutional Review Board (IRB). Both would almost certainly say no, based on lack of evidence to justify the trial. They would want preclinical evidence in cell culture and animal models, at the very least, or more compelling human evidence. You can provide me with neither. Of course, certainly I would be happy to review the educational materials you provide doctors who wish to administer Rigvir to patients. Maybe they would start to change my mind, although I’ll be honest with you and inform you that I doubt it. However, contrary to what you think, my mind is not closed. What it takes to open it more is high quality scientific and clinical evidence. Provide it, and perhaps it will convince me. If you continue to fail to provide it, and you’ll never change my mind. The ball is in your court. Sincerely Orac

Rigvir strikes back, round 3

The IVC didn't respond right away. It took a few days. Indeed, I was beginning to wonder if Ms. Lapa was going to respond again at all, particularly after nothing arrived immediately after my second post about Rigvir. Then, just as I was about to send a quick e-mail to tweak Ms. Lapa and see if I could get a response, this hit my e-mail in box:

From: Lelde Lapa < [REDACTED]@virotherapy.eu> To: [REDACTED] Subject: RE: Blog about RIGVIR Date: Tue, 26 Sep 2017 18:55:40 +0300 Organization: RIGVIR Development department Dear, Dr. Orac ...We are very grateful for every objectively critical remark that is addressed to RIGVIR and we always are trying to provide additional information to the source in order to improve objectivity. This time we however are relay surprised that someone who calls for scepticism and ask for proves, can easily believe to articles without any proven references or sources, that contains statement from people openly in conflict of interest and that is published in non-official portals in order to avoid responsibility for aspersion. And particularly we are sad that you was never interested in our position or in our facts that we openly offered and that are not published. During last month we have seen lots of false news and lies that was spread in Latvia in order to neglect RIGVIR, part of these news is spread under the name of respectable organisations. But unfortunately most of the stories does not have real authors. Most of this campaign is done via social networks so we need time to respond to attacks and we will inform you about the results. In the meantime we are open to organise professional seminars and conventions to share our information. For example, last Friday during the 8th Latvian Doctors Congress, satellite symposium about virotherapy and RIGVIR took place. Reports on clinical trials and post-marketing experience in clinical practice were presented to doctors. Around 5000 doctors were invited and everybody had chance to ask any question to our leading managers. We however received no question from the audience. Regarding rigorous clinical trials, most probably the definition has changed over time. For example the 1.st RCT ever was run just after the WWII. What we today call rigorous was defined only in the late 1990ies. While for example the FDA started requiring 5 year survival data for oncologic drugs, in the early 2000 those kind of data were still available only for a portion of NDAs. However A very direct outcome of WWII was that Latvia lost its independence. As a consequence, Latvia was literally thrown decades back, as well as held back, in all aspects of an advanced society. You may find that shocking to learn in 2017, but we can assure you that was a shocking "experience" already at that time on site. And it lasted for 50+ years. A slight and minor side effect, was that regulatory requirements did not adhere to the US framework. They were the so called Soviet style, which include lack of publication as well. Today, however, Latvia is part of EMA territory with the most up-to-date regulatory requirements. Therefore, the mode of showing efficacy has changed both over time and in space. Nevertheless, the requirements regarding efficacy were and are fulfilled. And this again is approved by the Ministry of Health of the Republic of Latvia that on 4th of September 2017 issued official statement supporting that RIGVIR is registered and included in the list of reimbursed medicines appropriately (see English translation enclosed) and here is in latvian source: http://www.vm.gov.lv/lv/aktualitates/preses_relizes/5507_par_zalu_regis… Regarding the use of Rigvir in Latvia. It may also come as a surprise to you that the medical records system in Latvia has not really changed since WWII. This, of course is not the companies responsibility. It may perhaps assist you in appreciating inclusion criteria used and the effort in managing the analysis published in Melanoma Research. When you discuss about our clinical trials or reproach us about lack of publications we are kindly ask you take into consideration also the economic differences between USA and Latvia fully into account, for example GDP per Capita in Latvia is around 15 thousand Dollars, while in USA it is 52 thousand Dollars or for example the whole budget for melanoma treatment of Latvia is around 0.7 MUSD. In other words you know how much those things costs and you should not judge from the stand point of the most advanced economy with the highest healthcare and science budgets. We are founders (Prof. A.Muceniece) family owned company that’s heritage is to provide this innovative treatment to any patient in the world who needs it and we will not discriminate any patient regardless from which clinic the patient comes. In your latest blog you have analysed part of testimonials about virotherapy with RIGVIR (Please note however that Ty Bolinger’s activates are not related to us). We have seen complains that stories of our patients was just coincidence or that there were other factors behind the survival. But what if we would provide you with many dozens of such testimonials and cases? Is there something at all to convince you? This brings us back to the offer to you - to try the medicine for your patient. For early stage patient they should use medical tourism to Latvia, but with late stages or in cases where there are no other treatment solutions, you might consider in application of extended use of non-registered medicine on-name basis to use the medicine in USA. Off course all the time with your supervision to monitor closely the efficacy. This means that it would be case analysis not a clinical trial. Due to work with EMA we would not initiate any activity with FDA yet, although we have preclinical and clinical evidences to start. We find this discussion, your blog and your activity in twitter really wired. If you suggest that there are better medicine for cancer patients, please use it. We have never limited anyone doing that. RIGVIR is a prescription medicine, patients cannot get the medicine by them self without doctor involvement. So to wrap up - if you would like to explore virotherapy and use it as a treatment, we are ready to cooperate with you and teach you about our evidences. But further correspondence and the exchange of opinions is not necessary any more. Sincerely, Lelde

Ms. Lapa (or whoever I've been corresponding with) might not think that an exchange of opinons "is not necessary any more" and that she can flounce off, digitally speaking, but I beg to differ. So, instead of responding right away, I decided that a public response would be more appropriate, to be unveiled this morning. So here's my response to Ms. Lapa. I'll be sure to send her a link to this after this post goes live. After all, why bother if the person to whom I respond doesn't see my response? So here we go. Here's my response written over the weekend:

Dear Ms. Lapa: You clearly don't know me very well if you thought I would not respond to this. Indeed, given what Rigvir Holding and the IVC are doing, I think it's a public service to show what you have been telling me to my readers. It's also not true that I am not interested in your position. If that were the case, I would never have bothered to engage in this lengthy e-mail exchange. That's the point. I've been trying to find out what evidence you have to support all the claims being made for Rigvir's efficacy in melanoma and other cancers. All that's indexed in PubMed is very thin gruel indeed when it comes to clinical evidence. It's not at all convincing. Yet you keep claiming you have this highly convincing evidence while making excuses for not publishing it and whining about people criticizing Rigvir on social media. Well, I have news for you: That's the world. Social media matters. You keep claiming that what's being said about Rigvir is false, but somehow you never actually bother to prove it to be false. And do you know how you could prove that it's false? Show us the data, just like drug companies in the US and EU have to do! So you had a satellite symposium on virotherapy at the 8th Latvian Doctors Congress. That's great, but not enough. A Google search shows that you had this conference but nothing about its results. Most satellite conferences publish abstracts of the work presented at the meeting, at least. Such abstracts are not viewed as being as convincing as a publication in a peer-reviewed journal indexed on PubMed, but they are at least something. After your conference, I am currently still left with nothing. It wouldn't even matter to me if the abstracts or conference proceedings were in Latvian. Show me the data! You claim to have clinical trial results and postmarketing results presented at this conference? Publish them! After my previous two posts on Rigvir, I'm sure that I can find someone to translate them if necessary. In the end, I can't help but wonder if your symposium was more of a marketing presentation than an actual scientific conference. Next, I do not need a discourse on the history of clinical trials and FDA requirements for approval of drugs, as I am well aware of that history and when the first randomized clinical trials (RCTs) similar to what we do now were carried out. I mentioned the 1962 Kefauver-Harris Amendment to the law creating the FDA mandated that the FDA to require rigorous clinical trial evidence of efficacy and safety simply to point out that evidence from high quality RCTs has long been a requirement for drug approval in the US and Europe. In oncology at first that meant measuring an endpoint known as overall (or objective) response rates (ORR), which measures what percentage of the patients treated demonstrate tumor shrinkage. Unfortunately, ORR is not a great surrogate for overall survival. So by the early 1980s, the FDA started to require evidence of improvement in OS. While it is true that these days, in order to speed up the process of drug approval, the FDA has been accepting surrogates for OS, such as pathologic complete response (pCR) and granting provisional approval for drugs that produce such surrogate endpoints, I note that Rigvir has no convincing published data supporting the conclusion that it can even meet those lower standards for provisional approval. I also do not buy your excuse that Latvia's medical record system hasn't changed since World War II. Believe it or not, until very recently, many US hospitals still used paper charts and relatively primitive record keeping. Many private practices still do. It took laws and incentives from the US government to prod our medical system into adopting electronic health records, and, even then, I note that we will probably never have the excellent centralized medical record systems that some countries in Europe do. As for your excuse that Latvia is a poor country. I counter that the very fact that Latvia is a poor country relative to the US and much of Europe is a very good reason that its government shouldn't be wasting money on cancer treatments whose manufacturer cannot produce strong evidence of efficacy! Yet, since I took an interest in Rigvir recently, I've seen claims that up to 70% of melanoma patients in Latvia are treated with Rigvir. In a country like Latvia, that is insanity if true! Think of what could be done with all that money if it were redirected to treatments that work! I also see Rigvir being advertised as effective against a wide variety of cancers when not even you have claimed to me that it is effective against any cancer other than melanoma. You claim that Ty Bollinger's activities are not related, but I don't see it that way. In making the long segment on Rigvir in Episode 3 of The Truth About Cancer (TTAC), Bollinger obviously had the full cooperation of the IVC's leadership. He brought Dr. Antonio Jimenez with him, who runs the quack cancer clinic Hope4Cancer and is now selling Rigvir in Mexico. He had access to your clinic and interviewed luminaries such as Dr. Ivars Kalvins, your medical director Dr. Kaspars Losans, and your director of research and development Dr. Peteris Alberts, as well as three of your patients. The resulting segment was highly laudatory and presented Rigvir as a miracle cure based on dubious testimonials. Like many cancer patients who found out about Rigvir from TTAC, I had heard very little about your virotherapy before TTAC was released and view the video series as the best marketing for Rigvir I've seen anywhere. Somehow, I doubt that you would have cooperated so much with Mr. Bollinger if you thought his segment would do anything other than praise Rigvir and the IVC the way it did. I conclude by again addressing your offer. I will be blunt. My opinion is that it is unethical, and I will not accept it. Basically, you appear to be paying for case reports that you can publish. My impression of this is backed up by this article on your website about grants for publications, in which the IVC announces that it is offering €5,000 "grants" for "publications on clinical studies of oncolytic virotherapy, observations or clinical cases in a publication that can be quoted in PubMed" and that the study "is intended on using oncolytic virotherapy rather than using oncolytic virotherapy in combination with other cancer therapies, medication etc." In other words, you want case reports or studies looking only at virotherapy, which, given the doubt about Rigvir's efficacy, would be highly unethical. I note that you also request that grant applicants "inform IVC on the publication topic and present to IVC the document draft before commencing the project and submitting it to the chosen journal." To me this sounds as though you expect the paper to be written, regardless of whether the study has already been done or not, but in fairness I will allow that the ambiguity could be due to a poor grasp of English on the part of whoever wrote this web page. Finally, before you express such disappointment with my blog posts and my activity on Twitter, I note that the Business Development Manager of Rigvir Holding, Kārlis Urbāns, has been attacking me on Twitter using fake news sources. He's been quite nasty. Here are examples:

Jā ļoti neatkarīgs Onkologs no ASV, kas nez kāpēc perfekti citē Latviešu valodu un jau iepriekš barojies no farmas - https://t.co/ENKPlndHFi

— Karlis Urbans (@kurbans) September 29, 2017

I note that he cites a post made by a notorious antivaccine blog, Age of Autism. I note that the bloggers at Age of Autism don't like me because I routinely skewer antivaccine pseudoscience. Here's another example:

Un cik nav fake itkā-onkologu vēstule?
Ir jau vēl daudz, piemēram, https://t.co/bBX9uS8IPg

— Karlis Urbans (@kurbans) September 29, 2017

TruthWiki is a fake wiki maintained by Mike Adams, who runs the quack and alt right (yes, both) website NaturalNews.com and got his start selling Y2K scams. The conversation after that is quite amusing, even though I can only read it through the stilted English from computer translation from Latvian on Twitter. I note that Mike Adams has been defaming me on his website for a year and a half now and is up to around 40 lie-filled posts about me. You'll excuse me if I don't take your lamentations about how mean and nasty I've been to the IVC seriously when the BDM and CFO of Rigvir Holding is quoting fake news sources that routinely lie about me and trying to portray me as a tool of big pharma out to destroy Rigvir. So to wrap up – if you would like to provide acceptable scientific and clinical evidence for the efficacy of Rigvir against any cancer, I am ready to cooperate with you and learn about it. Otherwise, further correspondence and the exchange of opinions are not necessary any more. Sincerely, Orac

After that, there's only one last thing to do:

oracknows Sun, 10/08/2017 - 21:36

Naturopaths: Able to turn even Epsom salt potentially deadly

oracknows — Fri, 06 Oct 2017 04:30:57 +0000

Naturopaths: Able to turn even Epsom salt potentially deadly

Naturopathy and naturopaths are a fairly frequent topic on this blog—and for very good reason. If there is an example of a pseudomedical "discipline" that has been gaining undeserved "respectability," it's naturopathy. It's licensed in all too many states, and physicians who have fallen under the spell of so-called "integrative medicine," a specialty that rebrands science-based lifestyle medical interventions as somehow "alternative" or "integrative" and uses them as a vessel to "integrate" quackery into medicine, seem to have a special affinity for naturopaths. Indeed, so common has the presence of naturopaths become in academic integrative medicine programs that I'm more surprised when I don't see one in a program than when I do. Sadly, even my medical alma mater, the University of Michigan, has a prominent "academic naturopath" (an oxymoron if ever there was one) on faculty, and the Society of Integrative Oncology has had not just one, but two, naturopaths as its president in recent years. Basically, doctors, particularly integrative medicine physicians with an MD, have pretty much zero clue what a cornucopia of vitalistic, mystical, pseudoscientific nonsense the vast majority of naturopathy is. The rest (diet, exercise, lifestyle) is nothing unique to naturopathy or anything for which naturopathy is required. Basically, to paraphrase the great Harriet Hall, what is good about naturopathy is not unique, and what is unique about it is not good.

That's why I periodically like to remind my fellow physicians what naturopathy really is. One way to do that is to point out the sorts of dangerous and unscientific practices embraced by many naturopaths. I saw just such an example earlier this week in, of all places, Ars Technica, in the form of an a story about a case report of a patient poisoned by a naturopath. How that naturopath accomplished the poisoning is something I hadn't heard of before, making this a two-fer, a reminder of naturopathic quackery and something new that I don't recall having seen before. I particularly like the title, Naturopath teaches real doctors something—a new way to cause liver damage. The case report tells the tale, Severe liver injury due to Epsom salt naturopathy. Of course, ccase reports are not in and of themselves necessarily indicative of a trend, but in this case, when taken in context with all the other things naturopaths do and the harm they can cause, this particular case report is a cautionary tale.

Epsom salt is basically magnesium sulfate, and Epsom salt solutions have long been used for a number of purposes. In this case a naturopath was using Epsom salt to dissolve gallstones:

A 38-year-old non-alcoholic, non-diabetic man with gallstone disease was prescribed three tablespoons of Epsom salt (magnesium sulfate crystals) with lukewarm water for 15 days for ‘stone dissolution’ by a naturopathy practitioner.

There is, of course, no evidence that magnesium sulfate can dissolve gallstones. Indeed, even compounds known to be able to dissolve stones, like ursodeoxycholic acid tablets, don't work very well and are almost never used. Basically, channeling my old general surgery knowledge, I know that asymptomatic gallstones are usually left alone. When they become symptomatic, that is usually an indication for surgery to remove the gallbladder, particularly if the patient develops acute cholecystitis or other complications of gallstone disease. Basically, gallstone disease is a surgical disease, to be watched if asymptomatic and operated on if it becomes symptomatic or causes complications.

The man treated by this naturopath did not do well:

He developed loss of appetite and darkening of urine from the 12th day on treatment and jaundice from the second day after treatment completion. The patient denied fevers, skin rash, joint pains, myalgia, abdominal pain, abdominal distension and cholestatic symptoms. Examination revealed a deeply icteric patient oriented to time, place and person without organomegaly or stigmata of chronic liver disease.

Jaundice, of course, is an indication of liver dysfunction, which can be due to obstruction of the biliary system or damage to the liver tissue itself (hepatocellular injury). Darkening of the urine is a sequelae of the elevated bilirubin levels in the blood that result in jaundice. The patient's blood chemistry values were consistent with hepatocellular injury as a cause of his jaundice. These lab values, however, are nonspecific and can only tell us that there is liver cell injury, not the cause. That required further tests:

Tests for viral hepatitis A, E, B, C, cytomegalovirus, Epstein-Barr and herpes simplex viruses and those for autoimmune hepatitis and IgG4 disease were unremarkable. There was no evidence of underlying sepsis and other organ failures. Contrast enhanced CT of upper abdomen revealed only hepatomegaly with mild periportal oedema. Percutaneous liver biopsy revealed submassive necrosis with dense portal-based fibrosis, mixed portal inflammation, extensive perivenular canalicular and hepatocellular cholestasis with macrovesicular steatosis and perisinusoidal fibrosis (suggestive of steatohepatitis) without evidence of granulomas, inclusion bodies or vascular changes suggestive of acute drug-induced liver injury (figure 1). Polarising microscopy did not reveal crystalline deposits.

Translation: There was no evidence for viral infection or autoimmune hepatitis, nor was there evidence of sepsis. The liver was enlarged. The biopsy revealed "submassive" death of liver tissue with inflammation and scarring. This resulted in cholestasis, the stasis of bilirubin in the biliary system. Steatohepatitis is hepatitis associated with fatty infiltration of the liver, often a sign of liver injury. (Alcohol, for instance, can cause the same fatty infiltration of the liver with inflammation, albeit usually much more chronically.) In other words, this man's liver was messed up.

Fortunately, the liver is an incredibly resilient organ. Cessation of Epsom salt intake resulted in the man's recovery, with his lab values returning to normal in 38 days. The authors note that Epsom salt overuse can cause diarrhea, electrolyte abnormalities, kidney injury, and cardiac arrhythmias. However, it can also cause liver injury:

Liu et al described the patterns of mineral-associated hepatic injury due to inhalational or intravenous exposure with pure silica, chromium-cobalt alloy and magnesium silicate (talc) in seven patients.3 They demonstrated that silica led to formation of sclerohyaline nodules within portal tracts and lobules in contrast to magnesium silicate injury that was associated with a predominant reactive fibrosis in portal and centrilobular areas. These patients were chronically exposed, in contrast to our patient who consumed Epsom salt in large quantities within a short period of time leading to predominantly necrotic and dense reactive fibrotic type of injury. Epsom salt-related severe liver injury and its histopathology have not been described in literature before. The Roussel Uclaf Causality Assessment Method (RUCAM) score was strongly suggestive of Epsom salt injury in our patient. We believe that underlying non-alcoholic steatohepatitis potentiated extensive liver injury in our patient, which resolved on stopping the offending agent.

Basically, the authors are explaining that what was observed in this patient was different from what is usually observed in patients with toxicity due to magnesium salts in that usually such toxicity is chronic, which results in fibrosis or scarring. In this case, the toxicity was acute and resulted in the death of significant swaths of liver tissue. Now, I will admit that I was not familiar with the Roussel Uclaf Causality Assessment Method (RUCAM) for liver injury. So I looked it up. It turns out that it's a system for assessing the likelihood that a given drug is the cause of acute liver injury observed. Points are awarded for seven components:

Time to onset of the injury following start of the drug
Subsequent course of the injury after stopping the drug
Specific risk factors (age, alcohol use, pregnancy)
Use of other medications with a potential for liver injury
Exclusion of other causes of liver disease
Known potential for hepatotoxicity of the implicated drug
Response to rechallenge

Total scores range from less than 0 to 14 with scores below 3 indicating unlikely, 4-5 possible, 6-8 probable, and >8 highly probable hepatotoxicity. The scale isn't that commonly used, because interpretation of some of its components can be a bit subjective, but it is useful for suggesting drug-caused liver toxicity, and clearly this patient had enough positives in his RUCAM assessment for his liver was highly suggestive that the injury was due to Epsom salt. Also, normally, when Epsom salt is used as a laxative, it's recommended that patients take 10-30 g in at least 250 ml water. This man was taking 45 g every day.

Edzard Ernst noted that this isn't the only serious adverse event that can occur as a result of excessive Epsom salt use. For instance, there is a case report of a fatality from hypermagnesemia (elevated blood magnesium levels) due to an Epsom salt enema administered to a 7 year old. Yes, a 7 year old.

Basically, naturopaths have advocated Epsom salt to "dissolve" gallstones for a very, very long time, even though there is no evidence that they are efficacious for this purpose. Whenever someone asks, "What's the harm?" I can answer: Right here. Whenever considering alternative treatments like this, it's important to remember that even benign substances (like Epsom salt) can be dangerous if used to excess. Unfortunately, all too often naturopaths think that, if a little is good (or at least harmless), then a lot will be better, and a hell of a lot better still. That's a major part of the philosophy of naturopaths, if you leave out homeopathy, and that's how you fry someone's liver with something as seemingly benign as Epsom salt.

oracknows Fri, 10/06/2017 - 00:30

False balance in reporting the case of a local mother jailed for contempt of court for reneging on an agreement to vaccinate her child

oracknows — Thu, 05 Oct 2017 01:38:54 +0000

False balance in reporting the case of a local mother jailed for contempt of court for reneging on an agreement to vaccinate her child

I sometimes like to write about things happening in my neck of the woods that are relevant to the kinds of things I normally blog about every day. This habit of mine dates back at least to the days when investigative reporter Steve Wilson of our local ABC affiliate used to lay down fear mongering barrages of nonsense about mercury in vaccines that would have made Robert F. Kennedy, Jr. proud if he ever knew about them. Then there was a report on "orbs" seen in photographs where the reporter speculated whether they were actual spirits. Then there's the periodic fascination with veterinary quackery that pops up on local newspapers and media from time to time, including reiki and acupuncture for Fido.

This time around, it's about vaccines. It started a week ago, when I saw this headline on the website of one of our own local news stations, basically Wilson's old stomping ground WXYZ, Metro Detroit mom could be thrown behind bars for not getting son vaccinated. Now there's a clickbait title if ever I saw one, guaranteed to inflame antivaxers andeven a lot of people who aren't antivaccine with the image of overweening state power throwing a mother in jail to force her to vaccinate. Hell, ad a couple of apocalyptic adjectives, and this could be a NaturalNews.com headline! Watching the video of the report and reading the text made me wonder if the malign influence of Steve Wilson's antivaccine "reporting" is still hanging around the WXYZ newsroom, even nearly ten years after he left.

So here's the story:

Basically, Rebecca Bredow and Jason Horne are divorced. Horne wants their children vaccinated. Bredow doesn't. A week ago, the case was in court, and Bredow was ordered by the judge to vaccinate her children within a week or face jail. (Spoiler that will surprise no one. She didn't vaccinate her children and yesterday was sent for jail for contempt of court. More on that in a moment.) Now, try not to grind your teeth as you read the first passage of the story:

If you have kids, their health, their safety is your top priority. However, what if doing what you think is best, could land you behind bars?

A Metro Detroit mother is facing jail time because of her beliefs when it comes to vaccinations and her kid.

"I would rather sit behind bars standing up for what I believe in, than giving in to something I strongly don't believe in," says Rebecca Bredow.

This isn't putting the reporter's finger on the scale (or producer's or whoever's responsible for this framing). It's dropping a brick on the scale on the side of the mother. She's basically painted as a martyr for her beliefs, and the portrayal continues throughout the entire story. In the video, there is even a voiceover during the interview, "Wow. Rebecca Bredow, what a position this parent has been put in." Elsewhere, the reporter, Andreana Isom, intones, Some may label this metro Detroit mother as overprotective, stubborn, strong, or...all of the above." Seriously? That voiceover was about as unprofessional as anything I've ever seen, on local or national media. As I watched, I felt a bilious gurgling in the back of my throat.

Then I saw this:

Rebecca tells 7 Action News that she and dad made the decision to space out and delay some their little ones vaccines.

"It wasn’t until they started grouping them together that I backed off of doing vaccines," she says.

Rebecca hit the books, educated herself, she says, on the research, literature and studies. She concluded that waivers were the best way to go, the best for her baby boy. After all, the state of Michigan offers that option, explains Joel Dorfman.

"We’re fortunate in the state of Michigan that’s still permitted, still allow religious, personal and medical exemptions for parents who chose to delay, to skip a vaccine to make various choices," says Doorman.

Rebecca and her ex-husband do not see eye-to-eye. Their conflict has become a court battle.

According to court documents. the child’s father wants their son vaccinated. Rebecca makes it clear where she stands on the issue.

A bloggers at the antivaccine blog Age of Autism or Thinking Moms' Revolution couldn't have portrayed Bredow more heroically themselves. Heck, just look at Ms. Isom at the end of the story, basically touting how brave Ms. Bredow is, about how she will fight going to jail, in order to be there for her children. Gag me with a spoon.

Come to think of it, I'm rather surprised that I haven't seen anything on antivaccine websites about this case, although I expect that will change now that this story has made national news and even international news, with a report on the BBC, which tells a different tale:

Rebecca Bredow would not let her nine-year-old be immunised after initially agreeing with the father to do so.

Her ex-husband has now been awarded temporary primary custody in order to get the boy the jab.

Michigan parents are legally allowed to skip or delay their children's vaccinations due to personal beliefs.

But Bredow fell foul of the law because she reneged on agreements with her former spouse dating back to November 2016 to have the boy immunised.

So now it becomes more clear. Horne and Bredow divorced in 2008 and shared parental custody, although Bredow was the primary caregiver. When they were married, apparently they were of the "Dr. Bob" Sears ilk of vaccine-averse, in which they wanted to "space out" the vaccinations. Reading between the lines, the father remained in that camp, but the mother became more and more antivaccine as the years went by and she did more of her "own research."

Sadly, even the BBC report indulges in false balance of a sort I thought to have been mostly banished from reporting on vaccines and autism in recent years, quoting a woman to whom I refer as the grande dame of the antivaccine movement, Barbara Loe Fisher, founder of the Orwellian-named National Vaccine Information Center (NVIC). In the case of the WXYZ ABC report, the false balance comes in interviewing a representative of a local antivaccine group, Joel Dorfman, without identifying him as such:

Rebecca hit the books, educated herself, she says, on the research, literature and studies. She concluded that waivers were the best way to go, the best for her baby boy. After all, the state of Michigan offers that option, explains Joel Dorfman.

"We’re fortunate in the state of Michigan that’s still permitted, still allow religious, personal and medical exemptions for parents who chose to delay, to skip a vaccine to make various choices," says Doorman.

Actually, Dorfman is (very) briefly identified in the video in a "blink and you'll miss it" caption as being a representative of Michigan for Vaccine Choice, but not in the accompanying online article.

So, yesterday, having failed to vaccinate her child, Bredow appeared in court again, as described in this Detroit Free Press story, Ferndale mom jailed for refusing to vaccinate her 9-year-old son, where we also learn that Bredow lied about claiming a religious exemption:

The court initially ordered the immunization Nov. 16, 2016, but it still hasn't happened. In between, Bredow cited religious objections.

But Horne's attorney said in court pleadings that the religious objection was phony arguing that both Bredow and her current husband, Gary, "testified that they do not practice the tenets of any organized religion," and calling a waiver document the couple filed with the child's school "a convenient lie."

Bredow said in court pleadings that her ex-husband has long known of her objection to vaccines and is only making an issue of it now because she's been attempting to collect back child support.Last week, McDonald issued an ultimatum, to Bredow.

"You have seven days to get your child vaccinated," McDonald told Bredow Sept. 27. "If not, you will appear here Wednesday and if you have not, I'll send you to jail. Let me say it one more time, you have seven days. It's ridiculous. Don't make me do that."

But when Bredow appeared in court today, the child still had not be vaccinated, and McDonald made good on her promise and ordered Bredow to jail.

First off, I don't understand why Bredow would have lied about religious belief to claim a religious exemption, given that Michigan allows personal belief exemptions to school vaccine mandates. In any case, the story sounds complicated. It also sounds as though Bredow either lied to the judge when she promised to vaccinate or later reneged on a promise to vaccinate. Either way, judges do not take kindly to that; so it's not surprising that Bredow is now spending a week in jail for contempt of court.

But what of Bredow's claim that Horne is only pushing the vaccine issue now because she has been trying to collect back child support? Certainly divorce and custody battles are often complicated, and it's rare that there aren't...issues...on both sides. Who knows? What I do know is that the reporting of this case has been sensationalistic and full of the false balance that used to irritate the hell out of me back in the day, when seemingly any story on vaccines would inevitably have an antivaxer interviewed for "balance." Unfortunately, the Free Press falls prey to this same trope:

Horne will have temporary custody of the child with an opportunity to get the boy vaccinated, a prospect that alarmed Joel Dorfman of Michigan for Vaccine Choice, a group that advocates for parents' rights to refuse vaccines.

"If this child is injured as a result of being given eight immunizations, who do you think is going to take care of the child?" Dorfman told the Free Press. "The judge?"

I've discussed Michigan for Vaccine Choice before. It was one of the sponsors of a visit from Del Bigtree, producer of the antivaccine propaganda movie VAXXED, in which Bigtree got—shall we say?—a bit overwrought, basically calling for armed rebellion against the government for forcing children to be vaccinated. Basically, Michigan for Vaccine Choice is rabidly antivaccine. Unfortunately, local media have elevated its status to that of a legitimate advocacy group, treating it not as the crank group that it is but as a group whose views are as valid as those of scientists and physicians who cite the evidence that vaccines are safe and effective.

Meanwhile,. antivaxers are sliming Jason Horne with memes like this:

As an aside, I can't help but mock the man, Joseph Sikora, for posting things like this:

Dude, it's "laboratories," not "labratories."

And this is his profile pic:

You get the idea.

Basically, local antivaxers are attacking Horne in a most despicable manner by claiming that the reason he wants his child vaccinated is because, if that child dies, he won't have to pay child support any more. Yes, they really are that depraved. Meanwhile, local antivaxers protested outside the court hearing.

It's never a good thing when divorced parents fight over custody issues. The child always loses. In this case, the addition of antivaccine beliefs only makes it worse, as the child's health care hangs in the balance. I suspect that this is only going to get uglier. I also predict that antivaccine groups will latch onto this case to portray vaccine mandates as fascistic assaults on American freedom. Cue Mike Adams. You know it's coming. I'm only surprised it hasn't happened yet. Maybe by the time this post goes live, it will have.

oracknows Wed, 10/04/2017 - 21:38

Why a case report being circulated by advocates doesn't show that the ketogenic diet combats cancer

oracknows — Wed, 04 Oct 2017 01:00:56 +0000

Why a case report being circulated by advocates doesn't show that the ketogenic diet combats cancer

It's October again, which is Breast Cancer Awareness Month. As someone who takes care of breast cancer patients, I have a love-hate relationship with October. On the good side, I like seeing positive messages about what's going on in breast cancer research, advocacy, and clinical treatment. On the other hand, the quacks come out. I also see a lot of bad breast cancer studies. You might think that I'd like that too because it provides blog fodder. I could actually do without that, but in this case I happened to come across a "study" that illustrates why I detest how those promoting unproven treatments prey upon the misconceptions and lack of knowledge the average person has about breast cancer. So it was when I encountered this on Twitter:

1) Study showing aggressive metastasized #breastcancer defeated with a #ketogenicdiet #lchf https://t.co/oWx7xngV1w

— Low Carb High Fat (@lowcarblonglife) October 3, 2017

With this followup:

Ketogenic diet was part of the Press Pulse strategy used as a complement to the normally ineffective chemotherapy.

— Low Carb High Fat (@lowcarblonglife) October 3, 2017

With this followup:

Ketogenic diet was part of the Press Pulse strategy used as a complement to the normally ineffective chemotherapy.

— Low Carb High Fat (@lowcarblonglife) October 3, 2017

I've written about the ketogenic diet before, specifically about how it is more hype than science right now. I just realized reading my previous post that it's been three years since I've done an in-depth post on ketogenic diets. Who knows? Maybe someone's published something more recently that might make me change my mind. However, if that's the case, it's certainly not a study like the one Tweeted above, co-authored by Thomas Seyfried, the guru of ketogenic diets whom we've met before.

As you might recall from the last time I discussed him, Dr. Seyfried is a professor of biology at Boston College, who’s pretty well published. He’s also working in a field that has gained much more respectability over the last five to ten years, namely cancer metabolism, mainly thanks to a rediscovery of what Otto Warburg discovered over 80 years ago. What Warburg discovered was that many tumors rely on glycolysis for their energy even in environments with adequate oxygen for oxidative phosphorylation, which generates the bulk of the chemical energy used by cells. I first described this phenomenon in more detail in a post I wrote seven years ago about a drug that looks as though its anticancer properties come from its ability to reverse the Warburg effect.

Unfortunately, Dr. Seyfried has also gone a bit off the deep end pursuing this idea, and the paper Tweeted above by him and co-investigators, as you will see. The paper is Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer. Sounds pretty serious, right? Unfortunately, this is just a case report, and it was carried out at a rather dubious clinic in Istanbul called the ChemoThermia Oncology Center, which specializes in combining chemotherapy with hyperthermia, which in and of itself is not quackery, albeit it is only potentially useful for a handful of cancers, where it's used in the form of hyperthermic intraperitoneal chemotherapy. However, in this case, what is being used is something called "metabolically supported chemotherapy" (MSCT), which was combined with a ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen (HBOT). So right there, just reading the abstract, my skeptical antennae started twitching. It sounds as though everything but the kitchen sink, but it's worse than that. Check out this passage:

In practice, MSCT initiates with a 12-hour fast, the application of pharmacological doses of regular insulin, and the development of mild hypoglycemia prior to the administration of chemotherapy. As was previously demonstrated in a case report of rectal cancer and a case series in pancreatic cancer, MSCT may enhance the cytotoxic effects of chemotherapy [4-5].

What they're talking about here is insulin potentiation therapy (IPT), which is not just unproven, but it's potentially dangerous quackery. The clinic itself touts case presentations that aren't even really case presentations, just pictures of shrinking tumors. I note that regular, run-of-the-mill standard-of-care chemotherapy can frequently shrink tumors, even metastatic tumors. What has to be shown is that this concocted regimen put together by the ChemoThermia Oncology Center actually does better than conventional chemotherapy. There is no evidence of that I can find anywhere on the website, but, a lot like the Rigvir website, there are testimonials and a crappy retrospective study.

But what about the case report itself? Well, let's take a look:

An overweight 29-year-old woman with a body mass index (BMI) of 28.1 presented with a lump in her left breast that was detected during a physical examination in December 2015. The patient was admitted to Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey in August 2016, with interval enlargement of the tumor. Magnetic resonance imaging revealed a 75 mm x 75 mm x 65 mm left breast mass (Breast Imaging Reporting and Data System Category 5) with irregular borders. Multiple lymphadenomegaly was seen in the left axilla with the largest being 27 mm x 20 mm. A Tru-Cut biopsy led to a diagnosis of a nuclear grade 2 invasive ductal carcinoma that was negative for ER, PgR, and HER2 receptors (Figures (Figures--44).

This is what we in the biz call "triple negative breast cancer" (TNBC). It's a subtype of breast cancer that tends to be more aggressive, like cancers with amplified HER2 receptor. The difference is that HER2(+) breast cancer can be treated with targeted drugs like Herceptin and Perjeta, along with chemotherapy, to great effect. Estrogen receptor-positive cancers can be treated with hormonal therapy, specifically drugs that block the action of estrogen. For TNBC there are not as of yet any approved targeted drugs. That just leaves cytotoxic chemotherapy. Also, note the extreme young age of the patient. Breast cancer is relatively rare under the age of 30. (I've only seen a handful of such patients over my 18 year career.) Unfortunately, breast cancer tends to be more aggressive in young women like this.

To translate the above: This is a 29-year-old woman with a large, locally advanced breast cancer with positive axillary lymph nodes (under the arm). That makes her at least stage 3 right off the bat. Unfortunately, it was worse than that. It was stage 4:

The patient was admitted to ChemoThermia Oncology Center, Istanbul, Turkey on October 1, 2016 and was evaluated using whole body (18F)-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT). The PET-CT scan revealed a 77 mm x 55 mm primary tumor in her left breast (maximum standard update value [SUVmax]: 22.65), multiple left pectoral and axillary lymph nodes (SUVmax: 11.44), multiple widespread liver masses (SUVmax: 30.34), and an upper left nodular abdominal lesion (SUVmax: 5.94) (Figure (Figure5,5, Video Video1).1). The patient was diagnosed with stage IV (T4N3M1) triple-negative invasive ductal carcinoma of the breast.

So, in addition to her local disease, she also had liver metastases and soem sort of upper abdominal mass. Neither of these were reported to have been biopsied, but, given their lighting up on PET scan, it's reasonable to conclude that they are metastases. However, here in the states, most oncologists would have biopsied one of the liver lesions to prove it.

So here's what happened next:

An MSCT protocol designed for the patient consisted of docetaxel (30 mg/m²), doxorubicin (20 mg/m²), and cyclophosphamide (250 mg/m²). This drug combination was administered following a 12-hour fast and the introduction of 5 to 10 units of regular insulin (Humulin R). Chemotherapy delivery was initiated at blood glucose levels of 50 to 60 mg/dL. With the patient’s written and informed consent, this therapy was delivered on the first and eighth day of a 21-day cycle for a total of four months. Insulin delivery and chemotherapy infusions were delivered after assessing blood glucose levels upon arrival at the clinic, and the insulin dosage was sufficient to lower her blood glucose to approximately 50 mg/dL prior to delivery of the chemotherapy drugs.

In addition to MSCT, the patient was encouraged to consume a KD. She received education regarding the diet restrictions and given food lists as noted in Table 1.

I'm a bit confused here. The standard of care is to give doxorubicin and cyclophosphamide together for a certain number of cycles, a combination referred to as AC (A=Adriamycin, the trade name of doxorubicin; C=Cytoxan, the trade name of cyclophosphamide). This is then followed by a drug related to Taxol, such as paclitaxel or docetaxel, administered as a single agent. The abbreviation of the whole regiment is thus ACT or AC, followed by T. I'm assuming that this is what this patient received, but the way it's written above sounds like they were given all together, which is not standard of care and would be expected to produce more toxicity. Certainly not standard of care is the IPT, nor is the KD. Nor is this:

The patient also received local HT and HBOT after each MSCT session. The OncoTherm EHY-3010 HT device (OncoTherm, Troisdorf, Germany) was used to gradually increase her body temperature to 45°C for each hyperthermia session (12 sessions, 60 minutes each) according to the manufacturer’s specifications. A mobile electrode measuring 40 cm x 50 cm was positioned on the thorax and abdomen that fully involved both the primary lesion and the liver metastasis. The Quamvis 320 hyperbaric oxygen chamber (OxyHealth, California, US) was used to produce an operating pressure of 1.5 atmospheres absolute (ATA; 12 sessions, 60 minutes each). The patient tolerated these combined therapies well with no evidence of toxicity or adverse events.

This is hyperthermia higher than is usually used, which is usually done at 41°-42°C They're doing 45°C, which is 113°F. That's at the very highest end of what is used.

At the end of her therapy, on February 20, 2017, the patient underwent repeat imaging, which showed nothing lighting up on PET scan other than the kidneys, which normally light up. Then in April, she underwent a modified radical mastectomy, which showed what we call a complete pathologic response (cPR) to chemotherapy. What that means is that, upon pathological examination of the resected breast and lymph nodes, no viable tumor cells were found. So this is as good a result as can be expected.

Now, our friend Tweeting above said, "normally ineffective chemotherapy." That is, of course, nonsense. If there's one thing about TNBC, it's that it's usually exquisitely sensitive to chemotherapy—at least at first. It's not uncommon to observe dramatic tumor shrinkage due to chemotherapy. What makes TNBC such a bad actor is that it tends to recur rapidly and develop resistance to chemotherapy. So, basically, it is not at all surprising that this woman had a dramatic response to chemotherapy, and there's no way of knowing whether the ketogenic diet contributed to her excellent response.

Yet, as we see above, this case report is being represented as a "miracle cure":

?Tks! I'm interested to know, but details like that don't seem to matter to #KetoBrigade for hailing it as near miracle cure for TNBC. Ugh. pic.twitter.com/HLEU5wXWf9

— Quidama (@IamBreastCancer) October 4, 2017

The authors also seem unduly impressed:

Given the poor prognosis and adverse effects, women with advanced TNBC may be counseled to forego conventional chemotherapy. This single case study presents evidence of a complete clinical, radiological, and pathological response following a six-month treatment period using a combination of MSCT and a novel metabolic therapy in a patient with stage IV TNBC. Given this patient’s remarkable favorable outcomes, further research and randomized clinical trials exploring add-on therapies (such as KD, HT, and HBOT) that may enhance the efficacy of traditional cancer treatments by exploiting the metabolic weaknesses in cancer cells are warranted, especially for patients with poor prognosis of high grade and/or late-stage cancer that is not expected to respond to treatment. Furthermore, this patient did not experience the adverse effects that are commonly associated with the current standard of care and this improved quality of life should also be considered when designing research that compares outcomes of MSCT, KD, HT, and HBOT to traditional treatment. In conclusion, this combined metabolic approach appears effective in treating advanced TNBC, given this patient’s complete response with a good quality of life.

Now, there is one thing that is interesting here. The doses of chemotherapy used were considerably lower than what is usually used, with doses decreased by at least half or more. Does this mean anything? Who knows? cPR rates for TNBC have been reported to range from 20-35%. It could mean the regimen made the chemotherapy more effective, or it could mean that this woman just happened to have a particularly chemosensitive tumor. Even if we take this case report at face value and accepted that chemotherapy efficacy had been improved, there's no way of knowing what did it. Was it the ketogenic diet? Was it the hyperthermia? Was it the IPT? (Actually, we know it almost certainly wasn't the IPT based on what is already known; certainly no studies of long term survival have been published.)

In any case, what we have here is a patient with stage 4 TNBC who underwent chemotherapy and surgery, showed a dramatic response, and then underwent surgery. She had a complete radiological response of her metastases (they were no longer detectable on imaging studies) and a complete pathologic response on her surgical specimen. She was alive six months after she started treatment. Assuming she's alive now, she's been alive a little more than a year with her diagnosis. That's nowhere outside the range of survival for stage 4 breast cancer, which has a roughly 20% five year survival. Indeed, extrapolating from what we know about neoadjuvant chemotherapy in TNBC (chemotherapy given before surgery), where pCR correlates with prolonged survival, it's not unreasonable to predict that this patient will do significantly better than the average patient with stage 4 TNBC. That this patient is alive now tells us nothing about whether the treatment used will prolong her life, and it certainly tells us nothing about whether everything larded onto the chemotherapy had anything to do whatsoever with her outcome. If anything, her excellent response is probably indicative of more favorable biology of her tumor than anything else.

Unfortunately, because most people don't know a lot about breast cancer or chemotherapy, this case report will sound very compelling to them.

oracknows Tue, 10/03/2017 - 21:00