Category: medicine

The Epstein-Barr virus appears to be an important cause of multiple sclerosis

January 14, 2022 • 9:15 am

The Epstein-Barr virus has been associated with a variety of diseases; as Wikipedia notes (my emphasis, and I’ve left in the footnotes so you can consult 11-13, which I’ve put in bold):

The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus.[2]

It is best known as the cause of infectious mononucleosis (“mono” or “glandular fever”). It is also associated with various non-malignant, premalignant, and malignant Epstein–Barr virus-associated lymphoproliferative diseases such as Burkitt lymphoma, hemophagocytic lymphohistiocytosis,[3] and Hodgkin’s lymphoma; non-lymphoid malignancies such as gastric cancer and nasopharyngeal carcinoma; and conditions associated with human immunodeficiency virus such as hairy leukoplakia and central nervous system lymphomas.[4][5] The virus is also associated with the childhood disorders of Alice in Wonderland syndrome[6] and acute cerebellar ataxia[7] and, based on some evidence, higher risks of developing certain autoimmune diseases,[8] especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome,[9][10] and multiple sclerosis.[11][12][13][14] About 200,000 cancer cases globally per year are thought to be attributable to EBV.[15][16]

Infection with EBV occurs by the oral transfer of saliva[17] and genital secretions. Most people become infected with EBV and gain adaptive immunity. In the United States, about half of all five-year-old children and about 90% of adults have evidence of previous infection.[18] Infants become susceptible to EBV as soon as maternal antibody protection disappears. Many children become infected with EBV, and these infections usually cause no symptoms or are indistinguishable from the other mild, brief illnesses of childhood. In the United States and other developed countries, many people are not infected with EBV in their childhood years.[19] When infection with EBV occurs during adolescence, it causes infectious mononucleosis 35 to 50% of the time.[20] In 2022, it has been shown that EBV infection increase the risk of developing multiple sclerosis by 32-fold.[21]

EBV infects B cells of the immune system and epithelial cells. Once EBV’s initial lytic infection is brought under control, EBV latency persists in the individual’s B cells for the rest of their life.[17][22]

Here are two EBV virl particles with some proteinaceous spheres (not nuclei!) containing the viruses’ genetic material.  I had mono about twenty years ago, so I’m probably carrying the virus, too.

It has spikes, like Covid-19:

Source

At any rate, note that the association with the virus (henceforth “EBV”) with multiple sclerosis (“MS”) has been suggested before (references 11-13, ref. 14 is this paper). I haven’t read the first three papers, but #14 is just out in Science, and I’ll mention it briefly today. It surely is, given the discussions, the strongest evidence to date for an EBV cause of MS.

The paper was called to my attention by the tweet below from Matthew. And, apparently, this is the strongest suggestion yet that EBV actually causes multiple sclerosis.  If this proves to be the case, and the evidence is pretty strong, then this opens the way to preventing MS, most likely via I suspect shots in the young, because once the diease develops, a shot wouldn’t work. In fact, Moderna is at this moment making an mRNA vaccine against the virus. (Although, coronaviruses like Covid-19 have RNA instead of DNA as their genetic material—EBV has DNA—it doesn’t matter what genetic material the virus uses to replicate, for the mRNA in a vaccine is used by the body to make viral protein that then activates the host’s immune system.)

One note: MS is a disease that appears when your immune system attacks the myelin sheath surrounding the nerves, which disrupts nerve impulses. That in turn can lead to multiple effects, including difficulty in breathing, walking, and seeing. All of us have known people with MS, and you’re probably aware that the disease varies widely in its severity, with of the afflicted dying very quickly and others living a life of nearly normal span. On average, MS takes away five to ten years from your life, and a lot of that life is unpleasant.

Here’s the tweet that alerted Matthew, and then me, to the new results:

The paper below with the nearly dispositive data is free; click screenshot for access or get the pdf here. The reference is at the bottom.

(There’s also a News and Views piece on this article, which you can get for free by clicking the screenshot):

Now the best way to see if the virus causes the disease is to inject virus-free humans with EBV, and see if the injected group gets MS more often than does a control (noninjected) group. But since 90% of adults are infected anyway, and this experiment is highly unethical, one has to find other ways.

These researchers did the next best thing: a retrospective analysis of blood serum left over from AIDS tests on more than 10 million U.S. military personnel.  The criterion for “causality” here is the philosophical one: A causes B if you never get B unless you have A beforehand. (This doesn’t mean, of course that A is the sole cause of B.) As the authors say, “causality implies that some individuals who developed MS after EBV infection would not have developed MS if they had not been affected by EBV.” Note that they say “some individuals”, as there may be other causes of MS. But this is more than an association study, as EBV negative individuals could be tested for infection status during their period of activity duty, and then screened for MS to see whether the disease is associated with earlier infection.

The ten million soldiers were screened over a period of 20 years, and the leftover serum, fortunately, had been stored.  All samples were analyzed for EBV infection and then the MS status of the individuals determined during the period of active duty.

5.3% of individuals whose blood were tested were EBV-negative (as I said, most of us are infected) and in a sample of ten million that’s about half a million people.

Among the personnel examined, 955 MS cases were identified, of which 801 cases had several blood samples available taken at differen times. For each one they looked at three serum samples taken BEFORE onset of the symptoms. Each case was matched with at least one non-MS-afflicted control individual of same age, sex, ethnicity, branch of service, and date of blood collection.

The results were pretty compelling. Under the causation scenario, you’d expect MS to develop almost entirely in the group that were initially EBV negative but then got infected, and only then did they develop MS.

And that’s what they found. To quote the paper:

Only one of the 801 MS cases occurred in an individual who was EBV-negative in the last sample, which was collected at a median of 1 year before MS onset [hazard ratio (HR) for MS comparing EBV-positive versus EBV-negative = 26.5; 95% confidence interval (CI): 3.7 to 191.6; P = 0.001, conditional logistic regression]. At baseline, 35 MS cases and 107 controls were EBV-negative. All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up, and all seroconverted before the onset of MS (fig. S3). The median time from the first EBV-positive sample to MS onset was 5 years (range: 0 to 10 years), and the median time from estimated EBV seroconversion, defined as the midpoint between the last seronegative sample and the first seropositive sample, to MS onset was 7.5 years (range: 2 to 15 years).

Remember, all of the 801 cases were EBV negative at the first sampling. Then all but one of the individuals who developed MS had gone from EBV negative to EBV positive. (The authors discuss the one outlier case, but you can read that for yourself.) To see if it was really EBV that was associated with the onset of MS, they looked at other viruses as well, and also looked at other disease markers that could show whether MS had already begun (but without physical symptoms) when the patients were still EBV-negative. (They didn’t find that.)

They did other tests as well trying (like good scientists) to try to rule out a causal role of EBV in MS. They ruled out “confounding by unknown factors” because of the strong association between EBV infection and later development of MS. No risk factor could account for the huge increase in MS propensity among those who went from EBV negative to EBV positive.

The other factor was “reverse causation”: perhaps EBV doesn’t cause MS, but the early development of MS, not detected clinically, could make a patient more susceptible to EBV infection. This is ruled out because only the EBV virus was associated with the pathology, while one would expect the “reverse causation” syndrome to make MS patients more susceptible to other viruses.  That wasn’t seen.

I won’t go on except to show this graph, which displays significant differences in the level of antibodies against various human viruses between controls and those who got MS (remember, these are all EBV negative people at the start of the trial.) The blue bars represented antibodies against viral proteins that showed higher levels in controls than in those who got MS, while the orange bars represent the level of antibodies  significantly higher in the blood samples of those those who got MS than the controls. As you see, the level of antibodies against EBV is much, much higher in the pre- and post-MS-onset blood samples than in the control (no MS) samples. In other words, no other virus beside EBV was associated with MS either before or after the symptoms appeared.

The last paragraph of the Science paper suggests MS therapy with monoclonal antibodies against the viral proteins might be better than current therapies, and in fact we’re using monoclonal antibodies now to help patients already infected with Covid-19.

But a better tactic would be not to get the disease in the first place, and the tweet below suggests a vaccine that might do this is in development. And if EBV is associated with all those diseases mentioned above, like cancer and inflammatory bowell disease then a jab when young might stave those off, too!

________________________

Reference:

Bjornevek, K. et al. 2022. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science,10.1126/science.abj8222(2022).

Guest post: Censorship at a Canadian Medical Journal

January 2, 2022 • 11:15 am

I received a long email from reader Leslie MacMillan, and I suggested that he turn it into a post for our readers. He kindly agreed. I asked him to write me a brief biography, which is below:

Leslie is a retired physician who worked as an academic clinician-teacher and in hospital practice.  Now in obscurity, he enjoys dinner with his family at a reasonable hour, playing the piano, and indulging his grandchildren.”

And here’s his contribution:

Canadian Medical Association Journal yields to external religious pressure, censors published letter

by Leslie MacMillan

The Canadian Medical Association Journal (CMAJ, “the Journal”) has retracted a Letter to the Editor following orchestrated religious pressure that accused the Journal and the author of “Islamophobia”.

“Islamophobia” is one of those words hurled at people without a definition of what it means.  Unlike many slurs, though, this one does have a definition.  “-phobia” means “fear of”.  A phobia can be irrational or it can be well founded.  Islamophobia, then, indicates only a fear of the implications of the tenets of Islam or the intentions of its adherents.  It cannot by the fact alone be equated with hate speech or, obviously, racism.  Yet it so often is.  Sometimes speakers will say, “tantamount to hate speech”, pulling their punches and evading the implication of an accusation of an offence under the Criminal Code of Canada and some other countries.  Fear can be thought of as unease or suspicion that professed views of love and tolerance are not sincere; it is then rational to withhold trust, the trust that liberal societies need to function.  If one is accused of Islamophobia, one ought to be able to respond, “Yes, I am.  Here’s why.”

For the cover page of its 8 Nov 21 on-line issue, the Journal used this stock photo.  There was no contextual link to any one article in the issue.  It seems to have been a generic free-standing cover photo in that it appears on the sidebar for each of the articles in the issue.

Dr. Sherif Emil, a senior academic surgeon in pediatrics at Montréal Children’s Hospital and McGill University wrote to the editor of the Journal objecting to depicting such a young child wearing a hijab.  He quoted Yasmine Mohammed, a Vancouver activist who has championed equality for Muslim women:  “The cover of @CMAJ features a little girl in hijab. How disheartening to see my so-called liberal society condone something that is only happening in the most extremist of religious homes.”   Emil then acknowledged his respect for the women he sees in his practice who wear the hijab—mothers and some adolescent patients.  He continued (direct quotations indented hereafter):

But respect does not alter the fact that the hijab, the niqab and the burka are also instruments of oppression for millions of girls and women around the world who are not allowed to make a choice. We are currently being reminded of this daily, as we see the tragic return of the Taliban in Afghanistan, and its effect on the subjugation of women and girls. Girls as old as those in the picture are being sold into marriage to old men — institutionalized child rape. The mentality that allows this to happen shares much with the one that leads to covering up a toddler. But even in so-called moderate Islamic countries, such as the one I grew up in, societal pressures heavily marginalize women who choose not to wear the hijab. In addition, women in these countries who are not Muslim and do not wear the hijab are often subject to intense harassment and discrimination. I know that because some of these women are in my family. I respect the women who see the hijab as liberating. But we must also remember the women and girls who find it oppressive and misogynistic.

Ironically, the article [which he interpreted the photo as referring to] explores evaluating interventions to address social risks to health. A young girl such as the one depicted in the image is typically also banned from riding a bike, swimming or participating in other activities that characterize a healthy childhood. She is taught from an early age, directly or indirectly, that she is a sexual object, and it is her responsibility to hide her features from the opposite sex, lest she attract them. A heavy burden for modesty is placed squarely on her shoulders.  So many women have been traumatized by such an upbringing, which, I believe, frankly borders on child abuse. Is that not a social risk to health? Are these children not a vulnerable population?

This link includes a citation to the tweet by Ms Mohammed quoted in the letter.  (Link found and posted by Retraction Watch commenter Andrew.)

The letter appeared in the Journal’s 20 Dec online issue under the heading, “Don’t use an instrument of oppression as a symbol of diversity and inclusion”, a form of words of the editor’s choosing, not the author’s.

Advocacy groups claiming to represent the interests of Muslims in Canada and Québec vigorously protested the publication of the letter and called for its retraction.  Dr. Emil received abuse personally on Twitter as well, as noted by Retraction Watch (q.v.)

The CMAJ editor responsible, Kirsten Patrick, apologized particularly for her choice of words in the heading.  The uproar, a lengthy happy-talk on why hijab is not oppressive, and the Journal’s efforts at damage control, are reported in a long CTV news article of 20 Dec from which I’ve taken a small snippet:

[Lina] El Bakir [Quebec advocacy officer for the National Council of Canadian Muslims] argues that publishing the letter was irresponsible, especially during a pandemic when doctors who wear a hijab are dealing with prejudices in their daily practice. . . .

A pre-written response to the CMAJ, included on the national council’s website as part of an online letter-writing campaign, cites a few sections in the Canadian ‘Medical Association’s Code of Ethics and Professionalism that medical professionals must adhere to.

“This article falls short of these standards,” the response states.

“We are asking CMAJ to retract this article immediately and issue a public apology before it does any further harm to a demographic that has been targeted by some of the most violent forms of Islamophobia in this country.  [Emphases mine,–LM]

The Canadian Medical Association itself, which owns and publishes the Journal, piled on with an official and gratuitous swipe at the author.

Islamophobia and other forms of hate [there’s that incorrect conflation again –L.M.] must not be tolerated in the health care profession or in our society. Like CMAJ, the Canadian Medical Association deeply regrets the harm caused by the publication of an opinion letter in CMAJ on Dec. 20, 2021.

CMAJ is operated independently of the Canadian Medical Association with its own governance structure and editorial board. While we will always uphold the editorial independence of CMAJ, we feel a responsibility to speak out and express our sincere apologies for the harm caused.

On 23 Dec., the Journal buckled to this pressure and not only retracted the letter but removed it from its website.  It made no visible effort to send the commentary to the author, publish some of it, and invite a response before doing so.  Click on the screenshot or read the text below.

The letter “Don’t use an instrument of oppression as a symbol of diversity and inclusion” (DOI: https://doi.org/10.1503/cmaj.80742; author: Sherif Emil)1 published in the Dec. 20, 2021, issue of CMAJ has been retracted by the interim editor-in-chief of CMAJ because the editorial process for the article was flawed and biased, and the letter should not have been published.

CMAJ acknowledges and is deeply sorry for the considerable hurt that many people across Canada have experienced from reading this letter. A formal apology from the interim editor-in-chief has been published at https://www.cmaj.ca/content/193/51/E1935.

Retraction Watch criticized the removal, contrary to guidelines from the Committee on Publication Ethics, which recommended marking it as retracted (as the PubMed copy is)

The author of the letter has posted his own conciliatory statement at the Canadian Healthcare Network here.

CTVnews reported further on 24 Dec:

Tabassum Wyne, executive director of the Muslim Advisory Council of Canada, [said] she was glad the CMAJ “took the necessary steps to correct that mistake” and hear from diverse voices. . . .The council had a virtual meeting with the CMAJ’s interim editor-in-chief, Wyne said, during which it was suggested that the journal look at anti-Islamophobia training in the future.

Wyne also expressed concerns about having anyone on the internet read the letter in an accredited journal.   “And that’s why we pushed so hard to have it retracted, and we’re happy with the results.”

It gets worse.  The CMAJ editorial group “seeks to remedy” the current lack of Islamic representation on its Editorial Advisory Board.  The Muslim advocacy organizations clearly seek to exercise prior restraint instead of merely complaining about it afterward.

The National Council of Canadian Muslims has since thanked the CMAJ for removing the letter, saying it appreciates “the efforts of the editor in chief for taking action and doing the right thing” and looks forward to working with her to “ensure this never happens again.”

(This CTVnews article misleadingly shows a photo of someone protesting Québec’s  laïcité law, la Loi 21.  This affair has nothing to do with that law and the author says he disagrees with it anyway.)

If the CMAJ follows through on this, there will be religious oversight of what an academic medical journal is permitted to publish.

Action

I have written the CMAJ and the CMA criticizing them for their lack of integrity in this episode. I encourage readers, particularly Canadian physicians, to do the same, even if you are not members of the CMA (as I am not), and even if you would not have published the letter in the first place were you the editor.  The Journal has received comments from readers mostly criticizing the decision to retract and censor —see the retraction e-letters link below—but I don’t see awareness of the undertaking to invite Muslim advocates to exercise prior restraint on publication.  This hidden censorship is especially dangerous.  I recommend that letters specifically call this out so the CMAJ knows you are watching.

Contacts for responding:

This site refers to the retraction announcement, not the original letter. You can submit e-letters there.

At this site you can contact the Canadian Medical Association.

John Locke argued that it is better for a society to be governed around religious tolerance because this would lead to less social disorder than for the state to enforce adherence to one religion and, necessarily, to suppress all others.  This works only if the religions themselves are compelled by secular laws to tolerate people who reject or even mock their every teaching—otherwise you have a state religion sneaking in the back door under the guise of stamping out (in this case) Islamophobia.

Growing up in secular Canada, I was always glad that believers could enjoy their freedom of religion but was even gladder that I enjoyed my freedom from religion.  Religious differences just never came up in ordinary or professional life.  The idea that someone should be enjoined from doing something because it offended someone else’s religious views, and that could be called “harm”, was unthinkable.  Increasingly it looks as if we risk losing this freedom out of fearful acquiescence of our institutions to intolerant and censorious religious pressure.  Islamophobia (my correct definition) afflicts them, too, and they don’t even notice it.  It’s up to us to open their eyes.

A funny title but a serious point about ivermectin and Covid-19

December 16, 2021 • 9:30 am

Reader Martim sent me a link to this article in The Economist, which is pretty much paywalled but includes a paragraph and two graphs you can see. Click on the screenshot below to see what’s viewable:

And the figures, which buttress the title’s assertion:

Just using Fisher’s Exact Test* on the directionality above (dots to left or right of line), the difference is not statistically significant, but it is in a suggestive direction. We need more data to see if this disparity is statistically significant and thus “real” (i.e. not produced by chance under an equal frequency null hypothesis).

Now this is basically all of the article I’m allowed to read, but it hints at why some studies may show a positive effect of Ivermectin on patients infected with Covid-19. To put it simply, worms are a “comorbidity”, that might be eliminated with ivermectin. If having worms makes raises your chances of dying or hospitalization from having the virus, then taking ivermectin could help save your life not by affecting the virus, but by ramping up your immune system after the worms have gone.  Ivermectin would not, then, be of any use in treating patients unless they’re known to be affected with roundworms. (Ivermectin helps get rid of roundworms that cause intestinal strongyloidiasis and onchocerciasis, conditions that weaken your immune system.)

The graphs above suggest what one might predict: ivermectin would be more efficacious against Covid-19 in countries with a higher prevalence of worms, specifically the kind of worms killed by ivermectin. And that’s what the graphs show.

Of course, some of the studies above, both positive and negative, may already have been discredited by subsequent inspection (I haven’t checked), but I’m surprised that nobody has suggested this explanation before. (If they have, I haven’t seen it.)

In a month or two we should know the results of the properly conducted Oxford study on the effects of ivermectin on Covid-19 mortality. I’m almost positive that if the drug does have a positive effect on the disease, it will be minor—certainly much less than that of vaccination or the new Pfizer antiviral pill. But we will wait patiently. I tried to bet my doctor on 3:1 odds (if I won, I’d get $10, while if he won, and Ivermectin had a big positive effect, he’d get $30) that ivermectin wouldn’t show a greater preventive or curative effect than jabs and the new treatments, but he rejected that as a “sucker bet”!

UPDATE: I’ve just managed to subscribe for free and so have seen the rest of the article; it appears that some have considered worms as a comorbidity. A quote (emphasis is mine):

Yet ivermectin’s advocates insist that there is solid science demonstrating the drug’s efficacy. One well-documented website lists and links to 65 different papers on the subject, many of which, on the surface, seem to support this claim. Could this many studies all be wrong? Recent analysis by Avi Bitterman, a dermatologist in New York, and Scott Alexander, a prominent blogger, suggests that the answer is nuanced. Ivermectin probably does help one subset of covid-19 patients: those who are also infected by the worms it was designed to fight.

Wading through the papers whose methodologies appeared sound, Dr Bitterman noticed that the studies that looked best for ivermectin tended to cluster in regions with high rates of infections by strongyloides, a parasitic worm. Common in much of Africa, Asia and Latin America, strongyloides can cause, among other things, diarrhoea, fatigue and weight loss. However, they only pose a graver threat if their numbers grow out of control. Such “hyper-infection”, which is often fatal, becomes far more likely if a patient is receiving corticosteroids, which both suppress the immune system and appear to make female worms more fertile. And dexamethasone, a corticosteroid, is now a standard treatment for severe covid-19, because it prevents the immune system from going into overdrive and attacking the body’s own cells.

Building on observations by David Boulware, a professor of medicine at the University of Minnesota, Dr Bitterman concluded that strongyloides may account for the conflicting results of studies about the effectiveness of ivermectin as a treatment for covid-19. In trials conducted in countries where the parasites are common, many people could have both covid-19 and strongyloides infections. Covid-19 might already have weakened their bodies’ defences against the worms; treating the coronavirus with corticosteroids would let the parasites run wild.

In the groups who received ivermectin during trials, the drug would keep strongyloides in check. But patients in control groups would be left at the worms’ mercy. This would make it look as if ivermectin were preventing deaths caused solely by covid-19, when in fact it was preventing those caused by the parasites or by a combination of the two infections. This mechanism would explain why most studies conducted in places where strongyloides are rare showed no benefit from taking ivermectin. “Ivermectin doesn’t treat covid,” Dr Bitterman wrote. “It treats parasites (shocker) that kill people when they get steroids that treat covid.” He concluded that “taking strongyloides endemic populations, putting them into a control group with corticosteroids is a death sentence”.

In July 2020 a group of doctors argued in the Journal of the American Medical Association that it was “reasonable to consider presumptive treatment with ivermectin for moderate- to high-risk patients not previously tested or treated for strongyloides”, and said that the risk of infection by the worms in covid-19 patients should be “based on factors such as country of origin and long-term residence”. The World Health Organisation also recommends ivermectin in this context. However, most people in rich Western countries like America—where demand for ivermectin, driven by advocates on social media, is so high that some people have resorted to taking the equine version of the drug—do not fit this description. At least when treating patients who have never been to countries with widespread strongyloides, the evidence suggests that mainstream doctors in such places are right to avoid prescribing ivermectin.

None of this, of course, suggests that vaccinations are less efficacious than ivermectin in preventing death from the virus alone, much less, as Bret Weinstein and Heather Heying suggest, you’re better off not getting vaccinated than getting vaccinated. Just get tested for worms if you get covid and live in a roundworm-infested part of the world!

 

*Note that Fisher has been canceled.

More about ivermectin!

December 14, 2021 • 11:00 am

I feel bad for this man and his wife, but there’s a strong dose of irony in this story from USA Today (click on title below to read):

An excerpt:

Keith Smith, whose wife had gone to court to have his COVID-19 infection treated with ivermectin, died Sunday evening, a week after he received his first dose of the controversial drug.

He was 52.

Smith was in a hospital in Pennsylvania for nearly three weeks and had been in the hospital’s intensive care unit in a medically induced coma on a ventilator since Nov. 21. He had been diagnosed with the virus on Nov. 10.

His wife of 24 years, Darla, had gone to court to compel the hospital, UPMC Memorial, to treat her husband with ivermectin, an anti-parasitic drug that has not been approved for treatment of COVID-19.

York County Court Judge Clyde Vedder’s Dec. 3 decision did not compel the hospital to treat Keith with the drug, but it did allow Darla to have an independent physician administer it. He received two doses before Keith’s condition grew worse, and the doctor halted the treatment. . .

. . .Darla sued UPMC to treat her husband with ivermectin after reading about similar cases throughout the country, all filed by an attorney in Buffalo, N.Y. She was assisted by a group called Front Line COVID-19 Critical Care Alliance, which promotes the use of ivermectin in the treatment of the virus.

He received his first dose on Dec. 5, two days after Vedder’s decision in the court case. After Keith received a second dose, the doctor overseeing the drug’s administration – a physician not affiliated with UPMC – ended the treatment as Keith’s condition deteriorated.

Here’s a photo of Keith and Darla; note the caption (click photo to enlarge):

Now there may have been nothing that would save this man once he was infected, and, after all, this is only one anecdote, not a disproof of the claim (made, among others, by Bret Weinstein and Heather Heying) that ivermectin is an efficacious preventive and cure for Covid-19. But I point out that we still have no good evidence that ivermectin can do either of these things, while we have strong evidence not only for the efficacy of vaccination (particularly with a booster), and now also for the new Prizer antiviral pill, which, if given within three days of the onset of symptoms, reduces the risk of hospitalization and death by 89%.  Even if ivermectin proves to have a marginal effect (and, given the studies, that’s the most it could have), it’s no match for existing treatments.

To see a summary of the “evidence”, read this short piece in Stat, a site for health and health-and-business related news (click on screenshot):

As I’ve already pointed out, many past studies purporting to show an effect of ivermectin were fatally flawed in different ways, including cases of apparent data-faking as well as post facto analysis without proper controls. Here’s a summary of the article above:

Where to look for higher quality data? A group called the Cochrane Collaboration spends its time conducting meta-analyses of the best-conducted clinical trials. After excluding dozens of ivermectin studies with “high risk of bias,” the collaboration left little room for optimism: “Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent Covid-19.” The group recommended that ivermectin use be restricted to clinical trials that might actually generate high quality data.

The World Health Organization and the Infectious Diseases Society of America concur. Even Merck, an ivermectin manufacturer, avers that there is “no meaningful evidence for clinical activity or efficacy in patients with Covid-19.” And just last weekend the FDA warned people not to use the drug as a treatment for Covid-19.

An FDA tweet. (Note: yes, people, I know that ivermectin has valid uses in humans for eliminating lice and parasites, so don’t bother to correct me. We’re talking about viruses here.)

Note that Stat reports that a properly designed study is in progress (my emphasis below).

Yet ivermectin boosters and merchants have convinced many to use this therapy for Covid-19, particularly in Latin America where its use is so widespread that researchers have had difficulty recruiting patients for trials of other potentially effective products. In June, YouTube suspended the account of Sen. Ron Johnson (R-Wis.), a member of the Senate Homeland Security and Governmental Affairs Committee, for a week for spreading misinformation about ivermectin and hydroxychloroquine.

I’ve also criticized Weinstein and Heying, who work in my own field, for not only denigrating vaccines, but pushing ivermectin. Those who heeded their advice have been put in danger.

The increased demand for the drug, combined with enhanced scrutiny from pharmacists, has caused shortages of veterinary formulations of the drug. Inevitably, a spike in calls to Poison Control Centers connected to the use of veterinary ivermectin has followed.

And the money paragraph:

The University of Oxford’s rigorously designed PRINCIPLE trial is now trying to determine if ivermectin actually benefits people with Covid-19. But until those results come in, I urge people to heed the lessons of hydroxychloroquine, bleach, and all the other purported Covid-19 cures: effective treatments will be identified through systematic scientific study, not by wishful thinking, fabrication, or miracles.

Remember the Hippocratic Oath’s dictum: “First, do no harm.”

If the Oxford study shows ivermectin has appreciable value in preventing or curing Covid-19, I will admit that I was wrong, though I reserve the right to judge whether such an effect is sufficiently strong to make the drug more valuable than current treatments.

Likewise, if the Oxford study shows very low or no value of ivermectin in preventing or curing Covid-19, I expect that Weinstein and Heying will issue a statement saying, “We were wrong. We may have put people in danger.”

But I can already say with assurance that anybody following their advice, dosing themselves with ivermectin and avoiding vaccination, is doing precisely the wrong thing.

Talking sense about the Omicron variant

December 1, 2021 • 12:00 pm

Reader Tom sent me this 19½-minute video about Omicron from health science expert and nurse John Campbell, who’s apparently been dispensing sound information on the coronavirus for a long time. Tom said this:

Dr. John Campbell has been my go-to-guy for the past 14 months on a nearly daily basis.  He’s lucid, authoritative, clear, concise and engaging, just a superb source of reasonable advice.

When I asked for more information because Campbell’s Wikipedia bio was scanty, Tom added this:

He’s had a YouTube channel since 2008 and is an evidence-based medicine proponent to the bone.  His videos are daily, usually about 20 minutes long and shot in a spare room of his home.  Just him wielding a sharpie, an overhead camera, printed sheets of the day’s topic and a calm, no nonsense discussion delivered in a clipped English accent.  No histrionics.  Like visiting a well-loved teacher during office hours.

Now remember, we know very little about this virus—neither about its infectivity or its virulence (which really encompasses severity and spreadability).  So take this with a grain of salt. However, Campbell readily admits our ignorance while claiming, with support, that this variant will be the dominant strain throughout the world.

He does sound a note of hope, i.e., the vaccinated, when infected with Omicron, seem to get generally mild cases, and hypothesis that its spreadability is negatively correlated with how sick it makes peope.

John also gives us a pessimistic timeline for a vaccination (early to mid-2022). He summarizes where all the cases are (everywhere), and the mortality rate (thankfully, zero).  Remember, it’s early days.

Sleepless in Chicago

November 14, 2021 • 9:15 am

Posting may be lighter during the next several weeks as I struggle to overcome a case of chronic insomnia (or “semi-chronic insomnia”) that started a couple of months ago but has been exacerbated (as is intended) by therapy.  I’m not looking for sympathy here—insomnia isn’t nearly as bad as many maladies—but I’m trying to explain why posting may decline in frequency and in quality for a while. (It’s hard to think and write on four hours of sleep per night.)

Backstory: I’ve had bouts of insomnia twice in my life, both associated with stress. One was at the University of Maryland when I began my first job and was anxious to make good.  The stress took the form of me being unable to get to sleep. I went to a doctor who prescribed a change in behavior. “If you can’t get to sleep,” he told me, “Get out of bed and do pushups until you’re worn out with them. Then get back into bed. Repeat every 20 minutes until you sleep.”

I suppose the idea was that I would get so revolted by having to do pushups that my body would force me to sleep.

It didn’t work: I was still an insomniac, but with an impressive set of triceps. Eventually the insomnia went away.  It turns out, though, that getting out of bed if you can’t sleep is the basis for the kind of therapy I’m trying now, called CBT-I, or “cognitive behavioral therapy for insomnia.” Everyone says that it has a high success rate (about 70%), and it doesn’t involve drugs, which I don’t like to take. (My doc and I have tried to find a good sleep doctor who knows about medication for sleep, but so far without success. And I don’t know if those drugs would be efficacious—some of them have the side effect of making you get fatter!)

My current sleep issues began about two or three months ago.  The issue this time was not getting to sleep, as I always dozed off within ten minutes of turning off the lights, but waking up early in the morning and trying, unsuccessfully, to get back to sleep. Sometimes I’d wake up at 1:00 a.m. and and struggle for hours to get back to sleep. (I’m told that many people had sleep disruption during the pandemic.)

I pushed my bedtime back farther and farther, until 8:30 p.m. (which of course puts a crimp in your social life), but all that meant is that I’d wake up even earlier.  I was getting about 5-6 hours of sleep per night, and I know from experience that I need at least 6.5 hours to function decently and 7-8 to be in top form. (And you supposedly need more sleep as you get older.)

As for the cause of this bout of insomnia, I have no idea. I’m not particularly stressed over anything, though when I (and many people) wake up in the middle of the night, worries and dark thoughts sometimes run through the head.  Eventually I trained myself to dispel this midnight anxiety by simply pushing the thoughts out of my head. But that didn’t help my sleep, either. I’d lie in bed awake thinking of nothing in particular, the hours would turtle by, and eventually I’d give up and get up for the day.

Finally, my doctor referred me to a psychologist who specialized in CBT-I, a method you can read about here. I’m told that the regimen will take 5-7 weeks, though it could be longer or shorter, and the rate of
“clinically significant improvement” in sleep (I’m not sure what that means) is about 70%.  Right now I’m starting with “sleep restriction”, which is BRUTAL. Here’s what the link says about it:

This method sets strict limits on the time you spend in bed. The initial limit used is the same as the amount of sleep you tend to get on a nightly basis. For example, you may only get five hours of sleep even though you spend seven hours in bed at night. Two hours in bed are spent trying to fall asleep or go back to sleep after waking up. In this case, your initial limit would be set so that you spend only five hours in bed at night. This means that you are likely to get less than five hours of sleep.

This sleep loss will make you even more tired at first. However, it will also help you fall asleep faster and wake up fewer times in the night. This will allow a solid period of sleep and a more stable sleep pattern. As your sleep improves, the limit on your time in bed is slowly increased. The goal is to reach the point where you get the amount of sleep you need without reducing the quality of your sleep.

For two weeks I kept a sleep log, recording bedtimes, waking-up times in the night (you can’t look at a clock, so you have to estimate), and what time I finally get out of bed, as well as how I feel the next day and whether I napped the previous day. Under the regimen above, NO NAPS ARE ALLOWED! That’s the toughest part—aside from feeling half-dead. Oh, and I need to exercise regularly as part of “sleep hygiene.” I’m taking very fast walks for several hours each week, but it’s not easy when you’re dopey.

From the sleep log, the psychologist determined that I was getting about six hours of sleep per night, including naps. Ergo, the prescription: go to bed at 8:30 and get up for the day at, yes, 2:30 a.m.  If you wake up in the night and can’t get back to sleep in 20 minutes, go into another room and read a book for five minutes. Then go back to bed. Lather, rinse, and repeat.  If you don’t get to sleep doing this, you still have to get up at 2:30 a.m.

Oh, and you aren’t supposed to be in bed for any purpose other than sleeping. That’s tough for me, as I always read in bed, write a lot of this site in bed, and am often horizontal when I’m home, even when awake. Now I don’t go near the bedroom until it’s time to sack out for the night.

You may have wondered how I know when it’s 2:30 if I’m not allowed to look at a watch or clock. I set my phone with an alarm. I’ve always hated alarms, and never used them since I always woke up at the same time. They’re intrusive!

They weren’t kidding when they used the phrase above: “this sleep loss will make you even more tired at first”.  The first day I got about 4 hours of sleep. And getting up at 2:30 a.m. is no picnic, let me tell you. There’s nothing on t.v., so I read or simply go to work. The second night I was so tired that I almost passed out, and slept the entire 6 hours without awakening. That was very encouraging, but last night was another 4-hour rest again. I’m not sure how long I can keep this up, but I’m determined to follow the regimen because it’s been shown to have a high success rate.

Well, all that is by way of explanation, but I also find the experience interesting though debilitating. But I know that lack of sleep can injure your health, so I’m worried about that, too.  The upshot is that trying to work or think or write often seem like insuperable tasks when you’re this tired, but I’m soldiering on.

Again, I’m not writing this to solicit pity (or prayers!), but to explain what’s going on.  I’ve found that just writing this down made me feel better—though not less tired.

Readers may wish to weigh in with their own tales of insomnia. (Please don’t prescribe things for me to do or swallow, though, as I want to stick with the plan we’ve settled on.) The disorder is said to be quite common.

NO LOOKING AT THE CLOCK!

It must be the full moon

November 5, 2021 • 8:25 am

Yep, the wackos are out: here’s a comment I got (but didn’t post) on my piece “Bret Weinstein and Heather Heying go unvaccinated for Covid, take and promote Ivermectin instead“. It’s from one Stephanie, who won’t be posting here again:

I have ivermectin and didn’t get it at an animal feed shop. It’s for human beings, prescribed by a human internist that treats Covid patients (a real living MD). He also prescribes it to ease vaccine side-effects. It helped mine, I had my period for months after the Moderna shot, along with neuropathy in my right arm which prevented me from working for 2 weeks. I did not follow up with a second dose and will not until at least third generation vaccines are available.You are a dangerous person and I challenge your view, your vaccine indoctrination. There are safe, healthy options for All and instead of promoting health, an MD’s ability to practice and prescribe, you support a billionaire class who wants you hooked into a booster program. You’re the laughable one, the one that should be shamed but you’re so insecure, you point at Bret and Heather

No control in her assertion of “it helped mine”, of course, and if she listened to Bret Weinstein and Heather Heying she wouldn’t have gotten the shot in the first place. If ivermectin is a “safe and healthy option,” why did she get a jab?

I stand by what I said: there is no convincing evidence that Ivermectin is either a palliative, a cure, or a preventive for Covid 19, much less a reliever of symptoms from the vaccination. There are mixed results from some studies of the drug, but those are almost all retrospective analyses, have pathetically small sample sizes, and many lack real controls.

We will have more definitive data in a couple of months. But regardless of that, we know that the shots are powerfully effective in preventing Covid, and, if you get it anyway, you get a milder case. Faced with the assurance of that result contrasted with our ignorance about Ivermectin, which simply cannot have as powerful a result as the vaccines, you’d simply be dumb to forego up the shots (which Weinstein and Heying have been urging; neither is vaccinated) and take a medicine designed for roundworms and head lice.

It’s not me who’s the dangerous person.