Articles

The Annals of Internal Medicine Qualifies for Fail Blog.

As most readers of the blog know, I am mostly an Infectious Disease doc. I spend my day diagnosing and treating infections and infectious complications. It is, as I have said before, a simple job. Me find bug, me kill bug, me go home. Kill bug. It is the key part of what I do everyday, and if there is karmic payback for the billions of microbial lives I have erased from the earth these past 25 years, my next life is not going to be so pleasant. I will probably come back as a rabbit in a syphilis lab.

It is always fun when my hobby, writing for SBM, crosses paths with my job. This month the Annals of Internal Medicine published “Oseltamivir Compared With the Chinese Traditional Therapy Maxingshigan–Yinqiaosan in the Treatment of H1N1 Influenza. A Randomized Trial.”

I though big pharma was good at coming up with names I do not know how to pronounce. If someone could provide a pronunciation guide in the comments, it would be ever so helpful, so I will not have to embarrass myself when this entry becomes a Quackcast. Dr. Hall wrote about this article on Tuesday, and I have avoided reading her post until this one is up, so there may be overlap in what is discussed.

What is Maxingshigan–Yinqiaosan (MY)? Twelve herbs, one better than the Colonel (and speaking of pronunciation, why is it pronounced “kernel”?) but lacking the spices. It contains

zhimahuang (honey-fried Herba Ephedrae), 6 g; zhimu (Rhizoma Anemarrhenae), 10 g; qinghao (Herba Artemisiae Annuae), 15 g; shigao (Gypsum Fibrosum), 30 g; yin- hua (Flos Lonicerae Japonicae), 15 g; huangqin (Radix Scutellariae), 15 g; chaoxingren (stir-baked Semen Armeniacae Amarum), 15 g; lianqiao (Fructus Forsythiae), 15 g; bohe (Fructus Forsythiae), 6 g; zhebeimu (Bulbus Fritillariae Thunbergii), 10 g; niubangzi (Fructus Arctii Tosum), 15 g; and gancao (Radix Et Rhizoma Glycyrrhizae), 10 g.

Quite the melange of products. Could there be antiviral or immunomodulating molecules in such a hodgepodge? Certainly. There is no a priori reason that Maxingshigan–Yinqiaosan would, or would not, have efficacy against influenza or its complications.

The reasons to test MY are partly appeals to antiquity, “Traditional Chinese medicine has been used to treat seasonal influenza for thousands of years,” plus a reference that, upon searching, does not contain the word influenza. Or pneumonia. Or respiratory tract infection.

You have to wonder, when you are in the second paragraph of the introduction and looking up the primary sources and they do not match the text, just how careful the researchers and the editors of the journal are. It’s the Annals. Not very. Which is why my subscription lapsed. And, to demonstrate just how infantile I can truly be, when I discuss the journal with residents, I pronounce it as if it had one ‘n’. But do not accidentally type in the url at work with Annals spelled with one ‘n’; I discovered our firewall filter has an Anals.org weakness.

In Europe, pandemic influenza has been recognized for perhaps 500 years: “Then suddenly, in July and August 1510, a ‘gasping oppression’ with cough, fever, and a sensation of constriction of the heart and lungs began to rage, seemingly everywhere at once.” And local flu has been known for maybe 650 years. Given those numbers, “thousands of years” seems a wee bit of hyperbole, especially when the reference doesn’t support the assertion. And as best I can tell from the Googles, no influenza was reported in China until the 1800s, and given traditional diagnostic testing modalities, I doubt they were looking at patterns of disease that would be identified today as influenza.

Then they say

In a recent meta-analysis of 31 randomized clinical trials including 5514 cases of influenza, the authors concluded that TCM had significantly increased clinical efficacy compared with placebo or no intervention.

And that analysis was? A systematic review of chuanhuning for acute respiratory tract infections. Chinese Archives of Traditional Chinese Medicine. 2007;25:2200-3.

The abstract said “There were 31 RCTs with 5514 cases were involved.” 5514 cases of acute respiratory tract infections, not 5514 cases of influenza.  Although I may be slapped down for this, as the original is in Chinese and there is nothing on the Pubmeds relating to chuanhuning.

Looking for the primary references of the systematic review as best as I could given the language issues, the Googles find “etiological diagnosis by clinical experiments and tissue civilization experiments show namely the product of inactivated influenza virus A type Ⅰ, Ⅲ type A, pneumonia, adenovirus (Adv) Ⅲ type, Ⅳ type, intestinal syncytial virus and respiratory syncytial virus (Rsv) have inactivation” and the few trials I could locate were for a hodgepodge of viral and other upper and lower respiratory infections.

Chuanhuning is not in the current regimen to be tested, and the authors of the systemic review mention “the evidence is not strong due to the general poor methodological quality.”

The argument, not supported by the references, for testing MY is: product A may work for influenza, so let’s try an entirely different product for influenza. Could the editors of the Annals be doing a worse job at reading the papers in their journals?

They then mention “Modern pharmacologic studies demonstrated that some TCM formulas had antiviral and immunomodulating effects (13, 14).” Reference 13 is Chen N, Ren L. [Modern pharmacology research and clinical use of max- ingshigan]. Academic Journal of Guang Dong College of Pharmacy. 2004;545-6. and reference 14 is Huang JM, Chen DP, Yang LP. [The immunomodulating effects of maxingshigan on asthma mice models]. Journal of Fujian Traditional Chinese Med- icine. 2003;34:38-9. At least both references have maxingshigan in the title, but whether the content matches the assertions, well, let’s say their credibility has not been demonstrated.

Of course, no study of “Eastern” medicine would be complete without the appeal to popularity:

During the early days of the 2009 H1N1 influenza A pandemic, the popular herbal formula maxingshigan–yinqiaosan was used widely by TCM practitioners to reduce symptoms.

Years ago, at conference, one of my attendings was being detailed about a new antibiotic, and the rep finished up with “and it is popular in Europe.” To which my attending replied “So was Hitler for a while.” A pre-Interweb version of Godwin’s Law.

Searching for Maxingshigan–Yinqiaosan in the Pubmeds yields little but the intriguing, yet unavailable, Two hundred and thirty-five cases of high fever caused by exopathogen treated with yinqiao maxing shigan tang.

I went through the tedium of searching each component of MY in the Pubmeds and its relationship to influenza and found nothing of note.

So the reason for the study, really, is that people were using it. Let’s see if it really works.

They randomized people with mild PCR proven influenza to

Oseltamivir, 75 mg twice daily; maxingshigan– yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan–yinqiaosan; or no intervention (control). Interventions and control were given for 5 days.

Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction.

It was not blinded, only a small flaw given the endpoint, and most patients did not receive an intervention until relatively late in the disease, when the impact would be lessened

In our study, the median time from onset of illness to randomization was 34.5 hours; 23.2% of patients presented 48 to 72 hours after the onset of symptoms.

Sooner is better with the treatment of all acute infections, and given the delay in therapy, they are approaching a natural history of disease study more than a therapeutic intervention study.

They found

Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan–yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan– yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P < 0.05) with oseltamivir plus maxingshigan–yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P < 0.38).

The actual numbers: control had fever for 26 hours, oseltamivir for 20, the MY 16 and the oseltamivir plus MY was 15, in real numbers the results are almost clinically irrelevant. And the treatment groups were randomized later than the no treatment group, and temperatures measurement started at randomization. So if the treatment groups have a head start in temperature measurement, that wipes out at mostly of the therapeutic advantage doesn’t it? Most of the difference due to when they started counting.

If you measure from symptom onset to resolution of fevers, you get

Control: 56 hours
MY: 51 hours
Oseltamivir: 55 hours
MY plus oseltamivir: 47 hours

It is the duration of illness that is clinically the important feature, so even if the effects are statistically significant, the difference is not clinically significant.  And besides fever, there was no improvement in other symptoms: “No difference in any individual symptom, including cough, sore throat, headache, or fatigue, was observed after treatment.” Fever often remits before other symptoms of influenza, and given the duration of illness, from a clinical perspective, none of the interventions did much of anything.

As to viral shedding

the median viral titer in throat swabs at enrollment was similar, and a rapid decrease in virus shedding was observed in all 4 groups (P < 0.001) Changes in virus shedding from baseline to day 5 did not differ by treatment group (P < 0.69 for time-by-treatment interaction).
Both baseline swab specimens and specimens collected on days 1 to 5 for evaluation of virus shedding were available for 148 participants. Compared with the 262 patients without viral shedding measurements, these 148 patients had lower symptom scores; a lower proportion of cough, headache, and fatigue; lower leukocyte counts; and longer time from onset of illness to randomization. Therefore, the virus shedding results from these 148 patients were not representative of the entire study population

But when you look at the actual curves,

there is separation between the oseltamivir containing regimens and those without, with the MY closer to the control. It suggests that the effect of MY is anti pyretic/immunomodulatory rather than antiviral. And given that the control group started the PCR measurements earlier as well, yo would expect slighly higher viral levels. If there is an effect from MY, it is a small one, and it appears to be less antiviral and more antipyretic, although the authors state

The study could not determine whether the observed effects of maxingshigan–yinqiaosan were due to anti- pyretic or antiviral effects.

I bet the former.

Given that the patients were all healthy, had mild illness and were treated relatively late in the disease, I would expect to any intervention to have a modest effect, and theirs was modest indeed.

Non sequitur central continues in the discussion where they discuss potential mechanisms of action and note

During the outbreak of the severe acute respiratory syndrome in Hong Kong, Poon and associates (24) showed that 2 herbal formulas had immunomodulating effects. In their study of healthy volunteers, they found that the CD4 –CD8 ratio of T lymphocytes was significantly increased after participants received Chinese herbal medicine for 14 days (24).

The reference, Immunomodulatory Effects of a Traditional Chinese Medicine with Potential Antiviral Activity: A Self-Control Study, states

We investigated the immunomodulating effects of an innovative TCM regimen derived from two herbal formulas (Sang Ju Yin and Yu Ping Feng San) for treating febrile diseases.

I am limited by language, variability in TCM medications and lousy editors at the Annals, but apparently Sang Ju Yin is Mulberry & Chrysanthemum Pills and Yu Ping Feng San, or Jade Screen Teapills, and neither have any ingredients in common with MY.

Sang Ju Yin and Yu Ping Feng San has to do with the mechanism of MY how? That is the kind of discussion the Annals has for its readers: randomness. Linear, logical thought appears passé these days. The authors seem to think all TCM are the same, and there is no reason to differentiate one TCM over another for mechanism of action: “More studies are needed to clarify the mechanisms of TCM.”

Me and my reductionist Western approach, thinking that different products, with different constituents, are actually different, with perhaps different, unrelated mechanisms of action, if they have a mechanism of action at all.

There were articles, again not available in English, that demonstrate in vitro effects of shigan on influenza A. That the references indeed demonstrate what the authors purport, well, I will have to trust the researchers and the editors of the Annals. They have done a fine job to date.

It would appear from one abstract, that 31.25 mg/ml of maxing shigan had multiple effects on viral replication in the test tube and that 31.25 mg/ml was the optimal concentration of the product.

In the study patients received 200 mL of MY orally 4 times daily. So for fun, assume 100% bioavailabilty. Lets assume 31.25 mg/ml in the preparation the patients received. Who knows. 200 x 31.25 is 6250 mg. A human volume is about 70,000 mls.  Assuming a uniform volume of distribution, that gives the concentration of MY at 0.089 mg/ml. Seems a wee bit below the needed MIC. Of course, a lot of assumptions in the calculation, mostly around the concentration of the medication, its absorption and the volume of distribution. The first and third were guesses, the second was probably a large overestimation (medications are rarely 100% absorbed). The real concentrations of MY are probably much less that 0.089 mg /ml.

50% alcohol will also inactivate influenza in vitro. Outside of a frat party, those levels are not achievable in vivo. Always the issue of going from in vitro to in vivo studies

The authors finish up with

In conclusion, in previously healthy young adults and adolescents who presented with uncomplicated 2009 H1N1 influenza A virus infection, therapy with oseltamivir and maxingshigan–yinqiaosan (alone and in combination) was associated with faster resolution of fever. Maxingshigan– yinqiaosan can be used as an alternative treatment of H1N1 influenza A virus infection when oseltamivir is not available.

and the abstract, which is all most people will read, ends with

These data suggest that maxingshigan– yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection

So here is where I am going to get picky.

My take, looking at the PCR data, is that MY does not treat influenza. There is no real change in the PCR viral concentrations. When you treat an infection, you kill it, or at least prevent it from reproducing. They did not treat influenza, they treated an epiphenomena of influenza, the fever. Treating fever is not the same as treating infection. And of course, it looks like the effect is an artifact of when they started counting, and given the lack of response of other symptoms, this is a mostly a natural history of influenza study.

And should you treat fever? Well, no. There is an interesting literature, with many a methodological issue, that suggests treating a fever is not a good idea.

In animal models and human studies, treating a fever is associated with prolonged illness and, depending on the study, increased mortality. There is no definitive study, but an hour of perusing the literature will show an interesting pattern. Fevers are usually good. Treating fevers is usually bad.

Fevers are an important and ancient response to infection. Most parts of the immune system function better at higher temperatures. Sometimes the patient lacks the physiologic reserve to cope with the metabolic demands of fever (poor cardiac or lung function) and strokes and heart attacks may be larger if the patient has a fever. So sometimes you need to treat fevers. But for most acute infectious diseases that have been evaluated, patients  and animals that have their fever suppressed are have a more prolonged illness, more complications, or increased mortality.

I never treat my kids fevers. They make less noise when they are 102 and will probably resolve their infection faster if I let the fever go, and that will get them to school and me to work that much sooner. Of course, when my wife takes over, she gives them Tylenol. No man is a hero to his valet. Not that my wife is my valet. It is a saying.

I could find no specific data regarding outcomes in treating influenza associated fevers, but I expect like most other infections, it would be a bad idea. And there is always that point in the inflammatory response where the beneficial effects are overwhelmed by the adverse effects of too brisk a response: SIRS, sepsis, TSS and the ever popular cytokine storm, although the fever per se is not issue in those processes.

What annoys, and concerns me at the end, is the confusion between treating influenza and treating the symptoms of influenza. The first was not demonstrated, the second perhaps was and is usually a bad idea.

Conclusion

The effects of MY on fever are probably not real, and if real are mostly clinically irrelevant and probably counterproductive for the treatment of influenza.

As to the mechanics of the paper (proper use of references, critical thinking), if it were from a college student, I would give it a ‘C’.  If it were from a resident on service? Flunk.

And the Annals? In my professional lifetime they have gone from a first tier journal to second tier to now? Now, I shed a tear. Almost as funny as Fail Blog.

Posted in: Basic Science, Clinical Trials, Herbs & Supplements, Science and Medicine

Leave a Comment (34) ↓

34 thoughts on “The Annals of Internal Medicine Qualifies for Fail Blog.

  1. Good heavens. That’s a bit of editing quite as incompetent as the recent case in the British Journal of General Practice. They published a rather interesting paper about “Acupuncture for ‘frequent attenders’ with medically unexplained symptoms: a randomised controlled trial (CACTUS study)”. It was interesting because it showed that acupuncture has no useful effect, not even a placebo effect.

    What’s crazy is that not only the authors, but also the journal, and the press release from the authors’ medical school, all claimed exactly the opposite. Peer review is almost completely broken.

    Details can be found at http://www.dcscience.net/?p=4439

  2. windriven says:

    “It suggests that the effect of MY is antipyretic/immunomodulatory rather than antiviral. ”

    It would be interesting to compare the regimens of Oseltamivir + MY with Oseltamivir + aspirin.

    But then as Dr. Crislip points out, treating the fever is not necessarily good medicine.

  3. elmer the fake nutritionist emailer not says:

    pronunciation (letter a in the following is always like the a in “father”): Ma-Sheeng-Shur (rhymes with “Fur”)-Gan Eeng-Chyow (rhymes with “wow”)-San

  4. TsuDhoNimh says:

    TCM had significantly increased clinical efficacy compared with placebo or no intervention A number of those herbs – as single herbs – have known anti-pyretic activity. So what is “amazing” that the mix of them brings down fever? Aspirin or acetominophen would have doen the same thing in a more predictable dose.

    All have anti-pyretic activity:
    Anemarrhena asphodeloides rhizome
    Artemisia annua
    Fritillaria thunbergii
    Radix Scutellariae
    Lonicerae Japonicae (flowers)

  5. inconscious says:

    Best opening paragraph ever.

  6. MS, MT(ASCP) says:

    I would not even give the graph above the time of day. There are no error bars, thus no way to estimate if vertical separation of values is statistically significant or not. There is also no indication of any kind of T-test performed. Were they hiding the truth of their data (i.e. it didn’t work) or ignorant of proper statistical analysis and presentation?

  7. nybgrus says:

    and speaking of pronunciation, why is it pronounced “kernel”?

    Stealing from the wiki and a blogpost on the topic:

    “The story turns out to be that the Italian word colonello, from Latin columnellus, the leader of a (military) column, got borrowed into French twice. The first time, it became coronel in French, possibly on the notion that it was from Latin corona ‘crown’ rather than columna.

    In modern English, the word colonel is pronounced similarly to kernel (of grain) as a result of entering the language from Middle French in two competing forms, dissimilated coronel and colonel. The more conservative spelling colonel was favored in written use and eventually became the standard spelling even as it lost out in pronunciation to coronel.”

  8. JPZ says:

    @Mark Crislip

    OK, I am going to take an odd tack here. I have been on an editorial board of a reputable journal. I can’t say that I have tracked down and read every reference of every manuscript I have reviewed. If the unknown referenced paper has reputable authors and jives with what I know about the field – I give it a provisional bye. If something unexpected is written and referenced, then I track it down for a read.

    I am in the process of writing a counterpoint manuscript right now, and I am taking more of your approach – look for defects and mis-citations anywhere I can find them. Some call it nit-picking, but I call it (and I suspect you would as well) fact checking.

    It is a different mindset and approach. You can fault the reviewers for the Annals with not showing more discernment or suspicion, but your approach and their approach yield two different products. But, as I write this counterpoint piece, I can agree that weak reviewing opens the journal and the reviewers to valid criticism. Also, the Associate Editor fielding the manuscript may not be all that familiar with the field of study and may rely too heavily on the external reviewers. Weak reviews can propagate toward publication in this way. I guess I am just trying to see it from the editorial point of view, even though I am doing some writing with the same approach you used.

  9. GLaDOS says:

    Yet another example of TCM causing brain damage in the physicians who decide to promote it.

  10. JPZ says:

    @GLaDOS

    Are you always this grumpy, or just here? You have said that you have had horrible experiences with CAM proponents undermining your prescriptions, but your venom seems particularly strong. Did someone die? I sympathize with having irresponsible fools undermining your credibility, but you might need to let that go. My experience is with being the PI of GCP/ICH clinical trials, but the one infanticide (post-partum depression related) and the few cases of child abuse I dealt with have marked me deeply as well. It took a while, but I found ways to move on without the hate.

  11. BillyJoe says:

    JPZ,

    You sound a little grumpy yourself :)

    I think it’s time to get angry.
    Or, at least, for some of us to get angry, while others play a more diplomatic role if they wish.
    In fact, I think both approaches are necessary to effect change.

    Blacks and women needed to get angry to force change, and then the actual changes were enshrined in law through the diplomatic efforts of others.

    (disclaimer: I lost the first fifteen years of my life to bullshit and another fifteen years gradually escaping the influence, and I’m not the least bit happy about those lost years)

  12. Th1Th2 says:

    I never treat my kids fevers.

    It seems you’re afraid to have your kids take your own medicine and untreated 102°F fever does not exist in your clinical practice. I see.

    It’s true. Doctors can never be trusted.

  13. cthuluforprez says:

    Great article Mark! Always a fan of your writing and a dedicated listener of Puscast and Quackcast.

    However, don’t get hoist with your own petard, sir.

    You wrote:
    ‘The reasons to test MY are partly appeals to antiquity, “Traditional Chinese medicine has been used to treat seasonal influenza for thousands of years,” plus a reference that, upon searching, does not contain the word influenza. Or pneumonia. Or respiratory tract infection.’

    Actually, this reference does contain the words influenza (pg. 148, 185), pneumonia (pg. 142, 148, 175, etc.), and respiratory tract infections (pg. 178).

    Otherwise, interesting read and insightful observations.

  14. GLaDOS says:

    JPZ,

    Integrative medicine doctors fail at thinking. My hypothesis is that believing six impossible things before breakfast actually causes some damage to the brain.

    It is not an unreasonable hypothesis. Just look at people trying to recover from prolonged cult membership. A lot of them really struggle with critical thinking and a basic sense of proportion.

    Of course it is possible the damage was there before the six impossible things. Still, it would be interesting either way, finding a correlation between executive deficits and being a moonbat.

    I would like to know how someone like Mercola would perform on the Iowa Gambling test.

  15. elmer the fake nutritionist emailer not says:

    “Moonbats,” huh?

    Well, that’s telling.

  16. GLaDOS says:

    Yes, moonbats –believers in magic healing powers, ancient Chinese wisdom, 9/11 being an inside job by the Jews and the Bush administration, stuff like that.

    Until I began talking to former cult members, I really had no appreciation for thought disorders induced and reinforced by social pressure. Generally, if a false idea is widely accepted by a person’s sub-culture, it’s not a psychiatric problem.

    But crazy due to cult is a real phenomenon, even though the psychiatrists largely ignore it.

  17. JPZ says:

    @GLaDOS

    My feeling is that your vitriol is still a bit on the strong side, but if you know former cult members and equate that to CAM – I guess I can understand that a little better. That is really worst case scenario in my mind, but I won’t deny that those worst cases exist. My impression is that they are few and far between, and the average homeopathist (for example) is just uninformed or misinformed. Now, your clinical experience may be with much more stubborn CAMers or with strident anti-”allopaths” (sp?) than mine, and I can’t put myself in your shoes for that one due to my lack of specialized perspective. But, your perspectives and experiences are very interesting when they don’t discourage intelligent responses.

  18. Mark Crislip says:

    My petard is not hoisted. The link is to a pdf that is a compilation of many articles. The specific paper has none of those words while the pdf does. Do you work for the Annals or sumphin? :)

  19. Mojo says:

    My petard is not hoisted.

    Well, it wouldn’t be: http://en.wikipedia.org/wiki/Petard

  20. GLaDOS says:

    JPZ, what’s with the vitriol vitriol vitriol vitriol vitriol?

    CAM is cult medicine.

  21. DW says:

    JPZ
    “My feeling is that your vitriol is still a bit on the strong side, but if you know former cult members and equate that to CAM – I guess I can understand that a little better.”

    You may have a slightly inflated idea of what a cult is? You’re picturing Jonestown or Waco or dopeyfaced Moonies on the street. Many cults are much milder and many ordinary people join cults. Cult psychology is a real thing and it isn’t something unusual or exotic; you probably work with or have family or friends who have participated in cults. It is a parallel phenomenon to CAM usage; it’s done by lots of people (especially baby boomers) who you would otherwise assume were quite rational (including highly educated people).

  22. cthuluforprez says:

    @Mark Crislip

    No. I do not work for the Annals. Would it really matter if I did (ad hominem)? I was following the link you provided. Why not just link the one paper that the Annals article was referencing? Or provide the name of the paper along with the link? Doing so would clear up any confusion. You could also provide a link the the paper you are critiquing so that an interested reader could look it up for him/herself.

    I’ll just do it for you…sir…

    For anyone interested, here is a link to the Annals paper:
    http://www.annals.org/site/collections/rct_pdf/0000605-201108160-00005.pdf

    The article Dr. Crislip meant to reference is entitled “Chinese medicinal materials and their interface with Western medical
    concepts” by Kevin Chan. It is the first article in the reference link.

    Problem solved.

  23. clare_hendry says:

    Hi

    Not being a medical practitioner, I’d love to know more about the pro’s and con’s of treating/not treating fever. I always thought the ‘sweat it out’ school of thought was an old wives tale. Also, what about the treatment in fever of young children (< 3 yrs)?

    Anyone have any links/references?

    Thanks

  24. Xplodyncow says:

    I though big pharma was good at coming up with names I do not know how to pronounce. If someone could provide a pronunciation guide in the comments, it would be ever so helpful, so I will not have to embarrass myself when this entry becomes a Quackcast.

    Did you mean “oseltamivir” or “maxingshigan–yinqiaosan” or both?

    Big-pharma molecule names are never pronounced how they look like they should be pronounced. A 5-syllable antiviral? Maybe “oh-sel-TAM-uh-veer”?

  25. jmcohen87 says:

    @Mark and anyone else with answers,

    you claim that oseltamavir gets rid of the virus and prevents people from becoming infected with it.

    1) Please provide a link where the effects are statistically and CLINICALLY significant…(not just a small difference because you seem not to like small differences).

    From Wikipedia:
    “On December 8, 2009, the Cochrane Collaboration, which reviews medical evidence, in a review published in the British Medical Journal, announced it had reversed its previous findings that the antiviral drug Tamiflu can ward off pneumonia and other serious conditions linked to influenza. They reported an analysis of 20 studies showed Tamiflu offered mild benefits in terms of duration of symptoms for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza.[14][15] These findings relate only to its use in healthy adults with influenza, not in patients judged to be at high risk of complications. Tamiflu may still be a useful drug for reducing the duration of symptoms, although for this use it still has yet to be compared with NSAIDs or paracetamol.[16]”

    2) Do you take issue with this review? Do you have a review from a different unbiased and credible organization?

    3) You claim that MY probably only affects just the symptoms. Your evidence is based on the fact that the Mean Viral Titer is less by oseltamavir than by MY. Is that difference statistically AND clinically significant? Also, is it significant that the MVT is initially higher by the MY group than both oseltamavir the control and ends up lower than the control?

    4) Also, how many other factors are there besides the MVT that indicate how much a virus has been weakened and how important is that singular factor (MVT)?

    5) “The effects of MY on fever are probably not real, and if real are mostly clinically irrelevant and probably counterproductive for the treatment of influenza.”

    I didn’t see you bring sufficient evidence for “probably counterproductive.”

    6) “So the reason for the study, really, is that people were using it. Let’s see if it really works.” Logically speaking, if people were using it and they claimed it worked against viral illnesses, why is that such a bad reason to conduct a study? And why are you attacking the reason for conducting the study so much? Even if they had no reason, if the study was well designed and MY had an effect then that’s all that matters.

    7) Have you taken into account the side effects of oseltamavir (there is a debate what they are and how significant they are but they still have some…)? You never even mentioned the issue of side effects. I think that’s important when evaluating two remedies against each other. Herbs generally have much less side effects than drugs.

    This site should be renamed Drugs Based Medicine. It seems like the most important goal on this site is to attack any natural remedy possible. Why is that?

  26. nybgrus says:

    @jmcohen87:

    1) The data actually isn’t all that great and that wasn’t the point of Dr. Crislip’s piece anyways. But instead of going to the wiki, you can just go to Cochrane directly:

    Neuraminidase inhibitors are effective in shortening illness duration in healthy children with influenza, but efficacy in ‘at risk’ children remains to be proven. Oseltamivir is also effective in reducing the incidence of secondary complications, and may be effective for influenza prophylaxis.

    or the BMJ meta-analysis:

    Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.

    So yeah, the data is not particularly striking. Once again, not the point but more so ties into your point #3.

    2) The issue with the review is not that the data is bad, but that the application of oseltamivir is difficult to attain properly in practice (see point 3)

    3) The differentiation you make of “statistically AND clinically significant” makes no sense. Clinical outcomes are evalutaed statistically and that is the metric by which we determine if the clinical difference exists or not. The MVT is also analyzed statistically to determine if the change in measured serum MVT is real or statistical artifact. If you are going to try and make a giant 7 point bash on the topic, with the distinct tone that you seem to know something about the topic, you should at least use your terms correctly. But I will assume you meant to say “does the statistically significant difference in MVT translate into clinical differences?”

    This is where the mechanism of oseltamivir comes in handy. When you are comparing things you must be comparing apples to apples. If you are looking at just clinical pictures and outcomes, then the mechanism makes little difference – you are seeing if MY and oseltamivir are changing the clinical picture. In this case we find that MY seems to reduce fever. In other words, it acts as an anti-pyretic (like aspirin or tylenol or ibuprofen). So the question then becomes, “How does it lower the fever?” Is it via an inactivation of COX pathways or is it because it is actually affecting the viral life cycle? Hence, a look at MVT is necessary to compare MY to oseltamivir.

    The mechanism of oseltamivir is blocking the release of viral particles. It is a neuraminidase inhibitor which prevents the sialic acid residues on the viral particles from being able to bind to the internal cellular membrane for release from the cell. So if the oseltamivir is working as it should, there should be a decrease in the MVT since more viral particles will sequestered in the cells. This will prevent more healthy cells from being infected and give the immune system fewer targets to destroy thus decreasing symptoms and duration. The probelm with oseltamivir is that once the infection is raging full on, and you have a boatload of cells infected AND a high MVT already, it really doesn’t do too much. It can’t prevent the viral particles from entering the cells, just leaving them. And since the flu is typically self limiting, by the time you get to that point the effects of oseltamivir are essentially masked by regression to the mean.

    MY did not demonstrate a decrease in MVT which means it did not work by the same mechanism. The rest of the data shows very minimal other effects, and when you look at the graphs and suss it out you find that the MY really didn’t do much of anything. Could it have done something? Sure. But unlikely given the data and methodology and the real point is the data did not support the conclusions and claims that the authors made, which is a big part of what Dr. Crislip was talking about.

    4) This is another question that belies your ignorance on the topic – oseltamivir does not weaken the virus. It doesn’t actually affect the virus in any way except to prevent it from binding and being released into the blood stream. So any measure besides MVT would be rather meaningless.

    5) Sufficient evidence for being counterproductive? How about the decades of clinical experience as an infectious disease specialist and the literature he references to demonstrate that fever reduction is actually counterproductive unless the fevers are so high as to induce delirum and/or seizures? You are throwing darts and hoping something will stick.

    6) The reasons for doing a study are very important, which you would undertsand if you were a regular reader here. As Dr. Hall puts it, there is too much “tooth-fairy science” out there. The only thing harder than getting the right answer is science is asking the right question so indeed, the reasons for doing the study are very important. Furthermore, the entirety of Dr. Crislip’s post demonstrates why it was, in fact, a very poor study and your blanket assertion that it was a good one simply falls flat.

    But even if it were a good study, the effects of MY are limited to being a mild anti-pyretic and maybe a mild immunomodulator. Forgive me and the rest of the rational world if i would rather take a few ibuprofen for the same effect but better and with less risk of side effects.

    7) There is no need to even look at the SE of oseltamivir for this synthesis – MY has not demonstrated it’s equivalence, let alone superiority to oseltamivir. In fact, the data show it doesn’t even act as an anti-viral in any way. You may as well ask to compare the SE profile of ibuprofen and digoxin. The paper claims that MY can be used instead of oseltamivir for H1N1 – that is not demonstrated. So comparing the SE is utterly pointless.

    Herbs generally have fewer side effects because herbs also generally do nothing, as we see from MY here. You can’t have a side effect if you don’t have an effect in the first place.

    8) [you didn't label this 8 but it is you last question] There is no systematic attack of natural remedies per se. However, most (actually the vast majority) of natural remedies do absolutely nothing or they do something a pharmaceutical already does but much less effectively. So why attack that? Because nobody knows what the hell is actually in a natural/herbal remedy. There are so many compounds in it that you are literally taking a pile of drugs that we have no idea their structure, function, side effects, interactions, etc for either no effect or a tiny version of an already undertsood and approved drug. Forgive me, but anyone rational would rather take 800mg of ibuprofen to lower their fever than tinctures of MY.

    So best case scenario is that the herb actually really does something. You know what happens then? It gets studied, purified, side effect profiles are decreased, and then a known, understood drug is released to the market. That is called pharmacognosy and is how many, many drugs are made. Taxol from the yew tree is a great example. Aspirin is a good one too. There is simply absolutely no benefit in chewing willow bark (or taking a pill of extract of it) over just taking an aspirin. Many drugs derived naturally like this are modified to reduce their side effects. Sometimes there are side groups added in order to make them more specific. Sometimes side groups are removed so that when they are metabolized in the liver the glucoronated or hydroxylated products aren’t toxic – BTW that one is pretty key; if you have an herb that “works” but then the metabolite is toxic… well, hopefully you get the idea. But this best case scenario is pretty rare, hence why pharma companies have to test literally hundreds of thousands of natural products to get one worthwhile drug out of it.

    Next we have the second best case scenario – it does something mildly well with few noticeable side effects. In most cases there would be a pharmaceutical already out there, the interactions and pharmacokinetics of which we already know, that would do a better job. So why bother? If there is no comparable one, then once again we are back to why on earth would you take the herb and all the other stuff in it instead of just purifying out the good bits?

    Then we have the “it does absolutely nothing” scenario with essentially no side effects. That is probably the majority of “natural remedies” out there. So once again, why bother?

    And lastly we have the “it does nothing AND has some side effects and interactions” which encompasses a large portion of natural remedies. And once again, why bother taking it?

    I suggest you watch “Would you eat it?” by c0nc0rdance on YouTube (I’d include a link but that would be my third one and the post would be held in moderation limbo so I will include it in a second post below).

    So hopefully that clarifies a lot of your questions.

  27. nybgrus says:

    apologies… the title was “Natural Cures” not “Would you eat it.”

  28. jmcohen87 says:

    Ahhh, the odious stench of dogma. I smell it almost as strongly here as I do on dr Mercola’s site.

    To start, I just want to say I identify as a skeptic. I am agnostic, I don’t believe in spirits or celestial beings. I don’t believe in energy medicine, homeopathy, or anything else that has been disproven or has no rational basis to go on.

    Next, some of my questions were genuinely to understand and not to attack. And you did enlighten me to a certain degree and I am grateful for that. Thank you. There were some ad hominems that I didn’t appreciate too much, but those are natural in debates, so I understand.

    Now to my retorts:

    1) No, it wasn’t my ignorance.
    “It is the duration of illness that is clinically the important feature, so even if the effects are statistically significant, the difference is not clinically significant.”

    Crislip is claiming the effects weren’t clinically significant ( I assume he means that the effect was too insubstantial) even though it was statistically significant. So I wanted to know if the effects of Oseltamavir was “clinically significant.”

    To know if the studies conclusion is valid – if MY can be used instead of Oseltamavir, we need to know if Oseltamavir is better – and even it is, by how much. I would argue we also should take cost and side effects into account. But you will reply that the study was only dealing with the effectiveness of 2 treatments and didn’t take those factors into account. Crislip rails against MY probably not being effective but doesn’t touch on the evidence that Oseltamavir is effective.

    3) Good points. You seem to accept the possibility that MY could have worked by some other mechanism, but then say that “it is unlikely given the data and methodology.” Why is that? Can you expound?

    4) Do you mean to say betrays my ignorance or belies my knowledge?
    And I was asking to learn, not to attack.

    5) I can bring decades of clinical experience of naturopaths, but that would be meaningless to you. Can you reference literature where an anti-pyretic herb was given and proved counter productive? Don’t reference literature with anti-pyretic drugs like tylenol. I know that stuff is junk. Let’s compare apples with apples.

    I would also counter that the duration of illness – or at least fever- was reduced. Correct me if I am wrong, but taking something like Tylenol reduces the symptoms in the short term but lengthens the illness overall. Did we see the same here? It seems like overall the fever was reduced, unless it came back again after the study was over….?

    “Forgive me and the rest of the rational world if i would rather take a few ibuprofen for the same effect but better and with less risk of side effects.”

    I love how you and SBM take up the mantle of skepticism and rationalism while dogma abounds. You both seemingly have entrenched views that cloud your rationality.

    You have no evidence that Ibuprofen is better or that it has less risk of side effects. I would guess that the sides effects are greater with Ibuprofen and would rather take MY. I am scared away when I look at the side effects on Wikipedia.

    6) I still don’t see why the reason is THAT important (I can agree it has SOME importance, but I think Crislip is overemphasizing it). Your answer wasn’t clear to me.
    I didn’t say it wasn’t a poor study. I just said the most important thing that he should deal with is the quality of the study. Instead he mostly dealt with the reasons to engage in the study.

    I still don’t see how you and Crislip are so confident that there were other mechanisms by which MY worked.

    7)” Herbs generally have fewer side effects because herbs also generally do nothing”

    I disagree that herbs generally do nothing, but proving our respective positions will be difficult.

    8) “So why attack that? Because nobody knows what the hell is actually in a natural/herbal remedy. There are so many compounds in it that you are literally taking a pile of drugsthat we have no idea their structure, function, side effects, interactions, etc for either no effect or a tiny version of an already undertsood and approved drug”

    According to that logic the same argument could be made about not eating carrots and other vegetables and instead just take vitamin A, vitamin E, etc..Why eat badly tasting vegetables when we don’t know the hundreds of chemicals in there. Let’s just take out the good stuff…Unfortunately, biology is more complex than that. And I will disagree with your fundamental assumption that herbs generally don’t work.

    I also don’t see how not knowing how it works makes much a difference as long as it does work. I do agree, however, that interactions with other drugs can be an issue. But that is as much of a reason against taking drugs as it is against taking herbs – as in let’s take herbs and refrain from drugs because it can interact with the herbs. The important issue is what is effective and at what cost in terms of SE’s. And I also think that we should study it and try to understand how it interacts with different drugs and herbs, but that isn’t a solid reason not to take it.

    9) I think we have fundamentally different views about herbs and drugs, which is likely influenced by our experiences. My fundamental assumption based on all that I’ve read – including lots of scientific literature – and all my experiences is that herbs generally DO work and the side effects are nill or insignificant. I will agree that it doesn’t always work the way it’s purported to work. But most of the time if it doesn’t work against a particular illness, it is still healthy in some other way, so the worst case scenario is generally pretty good. I also believe that drugs generally DON’T work (like the vast majority of drugs for cancer, AD, AIDS, dementia, MS, ALS and other chronic disorders) and if they do the effect on longevity is small and the SE’s can be very serious, which diminishes the quality of life (and did I mention the cost????).

    And many times when the effect is substantial, it only cures the symptoms and when you stop taking it the illness will rage even more than before and the SE’s are still serious. I believe that only in a very small minority of drugs do the benefits substantially outweigh the SE’s, and in the vast majority of those cases you have herbs that do a similar job with even less side effects.

    Proving these ideas either way will be difficult, but as you can tell our views are antithetical.

    Aspirin and Statins are good examples where they do more benefit than harm (although I don’t know enough about statins to say for certain), but you’ll have herbs that are just as good like Red Yeast Rice and Pycnogenol, with less side effects.
    I encourage you to read up more on Pycnogenol. They have done many clinical studies. Here is an interesting paper on it:
    http://www.kaire.com/mykaire1/pdf/pyc_Cardio.pdf

    That video is a disgrace to rationalism and skepticism. There are so many ways that I could pick it apart.

    This is the only clinical study done in America on RYR:

    Results: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice–treated group compared with the placebo-treated group [( ± SD) 6.57 ± 0.93 mmol/L (254 ± 36 mg/dL) to 5.38 ± 0.80 mmol/L (208 ± 31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly.

    Safety data
    "There were no serious adverse effects in any of the 88 subjects randomly assigned……."
    http://www.ajcn.org/content/69/2/231.long

  29. nybgrus says:

    @jmcohen87:

    I do apologize for my tone and any ad hominem that was tossed out there. I was writing very rapidly and am quite used to true believers coming out long after a thread has passed its time to espouse non-skeptical points of view. It is unfair, so I do apologize and you have geniunely given me a bit of insight into how I may approach such rhetoric better in the future.

    However, in reading your last two paragraphs I don’t think I was too far off the mark. I would not say we have two views, I would say you have the wrong view. I’ll expound on that.

    1) Whether oseltamivir is clinicall significant or effective actually doesn’t matter regarding this study. The claim was that MY was as effective or more effective than oseltamivir. The data failed to show that. So if oseltamivir is effective, then MY is still not as effective (and as Dr. Crislip demonstrates, not particularly effective at all) so why advocate its use over oseltamivir? I’ll get to that later on. But even if oseltamivir is not effective, then MY is still even less effective than that so either way MY loses and that is why establishing the efficacy of oseltamivir is a non-issue regarding the analysis of this study.

    3) Because the key issue here is whether it works as well or better than oseltamivir – that is the stated premise of the paper. It does not, so when you look at “some other mechanism” you find that it doesn’t suss out as being valid. Why can we say it doesn’t? Look back at Dr. Crislip’s assessment of the time of onset of symptoms, administration of MY, and time to resolution. You find that MY underperforms when the data isn’t manipulated to make it look like the MY shortened the course.

    4) This is where I have learned a point to take from the future. I assumed you were on the attack and that the mechanism of action of oseltamivir was something I would consider “basic homework” before asking questions like you did. I have learned from that and will not make such bad assumptions in the future. To return the favor though, when you don’t know the answer to such basic questions (which is perfectly reasonable) try not to ask 7 questions in one go, many of which hinge on an understanding of that one in order to formulate.

    5) You could also bring in the decades of experience of a plumber or a lawyer and I would also say those are irrelevant – and for a very good reason. Furthermore, the issue at hand is not an anti-pyretic herb – it is the concept of lowering a fever during an illness by any means. Dr. Crislip and the data indicate that it is not beneficial to do so. So whether it is via MY, tylenol, or aspirin, the point is the same.

    As for my comment about the herbs – that is not “dogma” that is realizing what you have very plainly not. That herbs are not this wonderful, safe, side effect free thing. I’ll address that further down below.

    6) Because the only thing harder than getting the right answer in science is asking the right question. Throwing a snowball at somebody may have an effect but that doesn’t mean it is worth looking at. In the case of MY many of the postulated reasons for its purported use turned out to be false – as Crislip pointed out, the references they used regarding its historical use as an anti-flu/viral treatment were simply false. To put it another way, a bunch of people can decide that eating dirt would be useful for colds and then cite a paper saying it agreed with the historical use. That citations turns out to be false. We then have no reason to study eating dirt for colds, both because the citation is false and because the very premise makes no sense.

    Why not just study it anyways, since heaps of people are doing it? Because the very nature of science and studies means there will always be a Type 1 error. So you will, by definition, always get some studies that show a benefit regardless of what you are studying. So why waste resources and confuse and conflate the evidence when the question you are asking is bad in the first place. That is why I say the only thing harder than getting the right answer is asking the right question and why Dr. Hall calls it “tooth fair science.”

    As for how we are confident that MY worked by some other mechanism is because it did seem to have an anti-pyretic effect, but clearly did not affect MVT. Hence, it cannot have lowered fever by decreasing viral burden (and thus the immune/cytokine response to it) but from some other method, much like currently employed anti-pyretics do.

    7) You can’t prove that herbs have fewer side effects, because you don’t know what is in the herbs in the first place. You are literally saying, “Here is a decoction which none of us has any clue exactly what is it in. But I am confident that is has fewer side effects than [X].” This is why your comment about “dogma” was so misplaced. We at SBM recognize this simple fact – that if you don’t know what is in it, you cannot say it has less side effects (or definitively say it has more, for that matter). The difference is that we recognize the vast majority of things that are biologically active will always have side effects. We also know that it is a vast minority of things that will have positive effects. So, when you combine those two things you realize that either a) there are no side effects because there are no effects or b) there are effects and side effects but the likelihood of them being positive are very low.

    You are correct that a similar argument could be made about foodstuffs and JPZ and I to have good debates about that very topic. There is very much a gray area as to when “food” becomes “drug.” However, in the case of herbals, we are definitely not in the food realm so your point is moot. I also say that when you concentrate foodstuffs such that you can take 10 times what a normal human could possibly consume in 2 pills, that has also left the realm of “food” and is now also a drug. So here, your argument loses vigor.

    You disagree with my fundamental assumption that herbs don’t work. Yet how do you reconcile that with the fact the pharmaceutical companies spend hundreds of billions of dollars sifting through every herbal, plant, and animal they can get their hands on to find something that works and come up with so relatively few? How do you also reconcile that with the fact that there is also no reason to assume that simply because something has a biological effect there is absolutely no reason to assume it would be a positive one? And further, how do you reconcile that with all the good studies and data out there on things like glucosamine, echinacea, gingko, vitamin C, etc that demonstrate they don’t work? I’m sorry, but this is simply a case where your fundamental assumption is incorrect.

    9) It is indeed influenced by our experiences – from what you have written here it is clear that mine is informed by my scientific knowledge and research background and yours is not commensurate. That is not an ad hominem, btw, that is merely an observation and statement of fact.

    My fundamental assumption based on all that I’ve read – including lots of scientific literature – and all my experiences is that herbs generally DO work and the side effects are nill or insignificant.

    There’s not much I can say here except that is simply incorrect.

    But most of the time if it doesn’t work against a particular illness, it is still healthy in some other way, so the worst case scenario is generally pretty good.

    Once again you are making an assertion without backing and completely not in line with the evidence.

    I also believe that drugs generally DON’T work (like the vast majority of drugs for cancer, AD, AIDS, dementia, MS, ALS and other chronic disorders) and if they do the effect on longevity is small and the SE’s can be very serious, which diminishes the quality of life

    Tell that to the patients I see on the wards who are still alive and doing amazingly well and thank me and the rest of the team for saving their lives. This is simply so wrong, it is not even right.

    And many times when the effect is substantial, it only cures the symptoms and when you stop taking it the illness will rage even more than before and the SE’s are still serious.

    Once again a completely evidence free and blanket assertion. Anytime you make such a broad generalization you can be pretty certain that you are wrong. And you are.

    Proving these ideas either way will be difficult, but as you can tell our views are antithetical.

    They really are not all that difficult to prove and have been. That is how I and the authors of this blog (and many of the commenters here as well) make the assertions we do.

    but you’ll have herbs that are just as good like Red Yeast Rice and Pycnogenol, with less side effects.

    Oh my, this one again (not from you, but it’s the red yeasty zombie that doesn’t die). RYR works because the yeast produces lovastatin. Yes, the exact same molecule that you think is so terrible is the exact same molecule in your RYR. The mistake you make is the naturalistic fallacy – which is why I referred you to c0nc0rdance’s video – in that somehow getting the exact same molecule, in an unknown quanity, with many other impurities, is somehow better than taking the pill from Pfizer or Merck.

    That video is a disgrace to rationalism and skepticism. There are so many ways that I could pick it apart.

    Then you really don’t know what you are talking about. I can assure you it is a very solid video brought down to the average lay person level of understanding and that c0nc0rdance is actually a very serious scientist who knows what he is talking about.

    “There were no serious adverse effects in any of the 88 subjects randomly assigned…….”

    So you want to quote a study that shows a statin works (produced by a yeast instead of a well regulated company) and give me a sample size of eighty-eight and call that demonstrating superior safety? I am beginning to think some of my ad hominem was quite warranted.

    I believe that only in a very small minority of drugs do the benefits substantially outweigh the SE’s, and in the vast majority of those cases you have herbs that do a similar job with even less side effects.

    Your belief is unsubstantiated. And more so you compared the SE profile of say, aspirin, with an herb and claimed that it is massive for the former and minor for the latter. That is not because there are less side effects – that is because we actually have studied and know the SE of aspirin. We don’t know anything about the herb in question. So once again, you are pointing to a black box and asserting it has qualities (or lacks negative aspects) without any possible way of knowing that and then pointing to a really well known and studied drug and commenting how big the SE list is. If you can’t see the fallacy there and understand why that makes no sense, then there isn’t much more to discuss.

    But hopefully you understand a bit more and will amend your beliefs to match the evidence and reality.

  30. nybgrus says:

    ah crap. Sorry for the formatting error with the blockquotes… should still be understandable though

  31. Nescio says:

    jmcohen87

    My fundamental assumption based on all that I’ve read – including lots of scientific literature – and all my experiences is that herbs generally DO work and the side effects are nill or insignificant.

    Like birthwort for example?

    For thousands of years birthwort (Aristolochia clematitis) was highly regarded by herbalists both in Europe and in China, and was prescribed for a wide range of conditions, including difficult childbirth. It was only scientific study that revealed it damages the kidneys and is carcinogenic. We can only speculate at how many people over the years have died from kidney failure or cancer as a result of taking birthwort.

    We can also only wonder how many herbs are in widespread use that are also toxic to a greater or lesser degree. Would you know if 1 in 1000 people who takes a herb you prescribe develops kidney failure as a result? 1 in 100? How?

  32. JPZ says:

    @jmcohen87

    An outcome that is statistically significant but not clinically significant is near meaningless in the treatment of a disease – Mark Crislip is absolutely right. I could design a study large enough to detect the difference in disease duration to +/- 10 min. Is a 95% chance getting better 11 minutes faster after 7-10 days of the flu meaningful to you physically (well, assuming you didn’t need to pee right then…)?

    On a statistics note: I’ve heard the Nurse’s Health Study data (n=35,000?) can be used to prove that someone born in Sagittarius has a higher risk of dying of a heart attack on Mondays (not that exact one, but several that sounded that crazy). I am interested in TILIS’s reply if it is under four paragraphs (LOL, sorry – the replies are getting a bit long again, but no less insightful).

  33. jmcohen87 says:

    I’ve been meaning to reply but it would’ve been too long and by the time I had the chance the topic got stale. But here is a welcome contrast to drugs based medicine (this site) and science based medicine. This site is biased and this man isn’t. He also mentions oseltamavir, which is why I am posting it here…

    http://www.youtube.com/watch?v=h4MhbkWJzKk

Comments are closed.