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March 2018 Short Takes from Doc Gumshoe

Baking soda, Alzheimer's, oncolytic viruses, measles, and more...

By Michael Jorrin, "Doc Gumshoe", March 29, 2018

[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investment ideas. His ideas, thoughts and words are his own, and you can see all his past pieces here.]

A projected winner hits a snag

No sooner had the Doc Gumshoe dossier about the 2017 FDA approvals posted than a bit of bad news surfaced about one of those winners.   AstraZeneca’s Imfinzi (durvalumab) was approved for the treatment of urothelial carcinoma (an advanced form of bladder cancer), and was projected to bring in about $2.8 billion.   Imfinzi was being evaluated in a Phase 1 / 2 study as part of combination therapy in HPV-associated cancers with a new agent from Advaxis, axalimogene filolisbac.   The short take version (and I did promise short takes, didn’t I?) is that after five doses of the combined therapy, which went just fine, a patient with advanced refractory metastatic cervical cancer developed respiratory failure while receiving the sixth dose.   Despite efforts to reverse her worsening condition, the patient died.

Based on previous data in studies with Imfinzi, it seems somewhat likely that the cause of the patient’s respiratory failure and death was Imfinzi and not the Advaxis agent.   One patient in AstraZeneca’s Phase 3 trial of Imfinzi in lung cancer had died of respiratory failure.   That, by itself, should not be definitive proof that Imfinzi was the cause of death; the patient, after all, did have lung cancer.

In any case, the FDA stopped the Advaxis combo trial, and at this point they’re trying to figure out what to do next.   The Advaxis agent, axalimogene filolisbac, is a proposed cancer vaccine based on Listeria monocytogenes, a bacterium that can cause meningitis in susceptible individuals, mostly immunocompromised children and the elderly.   (Needless to say, the bacterium is modified so as to be relatively harmless.)   The Listeria bacterium is taken up by cells that are active in the human immune system such as phagocytes, and can induce both CD4 and CD8 antigen-specific immune response.   Thus, it is a promising candidate as a cancer-vaccine vector.

Whether this incident has any major implications for Imfinzi remains to be seen.   However, this is an illustration of the perils that pharmaceutical outfits run even after FDA approval.   It is usual that a pharmaceutical company would look for other indications after a drug had been initially approved in a fairly narrow slot.   This is particularly the case with cancer drugs, which typically – these days, anyhow – get approval with very narrow indications such as relapsed or refractory cancers with a specific genetic footprint.   But the hunt for broader indications has its risks.

(As we’ve discussed in previous installments, the only way a prospective cancer drug could gain approval for a broad indication such as solid tumors would be to go up against an established drug in a head-to-head trial and be shown to be superior.   That would be hugely risky for the prospective candidate, and the FDA would be highly unlikely to approve a trial where half the patients got an untried drug when an established drug is available.)

More about oncolytic viruses

The term “oncolytic viruses” is, all by itself, an expression of optimism.   The “onco” part refers to tumors, and the “lytic” to lysis, or dissolution.   An oncolytic virus is thus, by this optimistic definition, a virus that dissolves tumors.   Are there any such?

The answer is an unequivocal “Yes!”   The first FDA-approved oncolytic virus was Imlygic (talimogene laherparepvec), from Amgen, which got its seal of approval on October 27, 2015, with, as is usually the case, a fairly narrow indication: “Indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.”

It has been known for some time that some viruses preferentially attack cancer cells rather than normal tissue, but this by itself does not make even those viruses into ready-for-action cancer fighters.   Even those viruses are likely also to infect normal tissue.   As a rule, viruses need to be genetically modified such that they attack tumors while leaving the human host unharmed.   Imlygic is such a virus.   It is a genetically modified herpes simplex virus type 1, designed to replicate within tumors and produce the immunostimulatory protein granulocyte-macrophage colony-stimulating factor (GM-CSF). It is injected directly into the melanoma lesions causing the cancer cells to rupture and dissolve. This in turn releases tumor-derived antigens, which, along with GM-CSF, promotes an antitumor immune response.   In other words, what the herpes simplex virus does, after it has been tinkered with, is direct the body’s own immune system in such a way that it targets and attacks cancer cells.

Having gained its first approval for Imlygic, Amgen is not stopping there.   Currently there are 35 clinical trials with Imlygic, underway or in the recruiting phase.   Many of these are in combination with other drugs that have demonstrated some efficacy in treating cancer.   The cancers being targeted in these trials include pancreatic cancer, non-melanoma skin cancer, some cancers in children, breast cancer recurrence and triple-negative breast cancer, some bladder cancers, rectal and colorectal cancers with liver metastases, and squamous cell carcinomas.

Imlygic is based on the herpes simplex virus, but several other viruses are being investigated for their oncolytic properties.   Canadian researchers have found that the Maraba virus, part of the rhabdovirus family, can replicate inside triple-negative breast cancer tumors in mouse models.   The virus, when used along with a checkpoint inhibitor, eliminated the tumors in more than 60% of the mice.   By itself, the checkpoint inhibitor was entirely ineffective.   The Maraba virus is considered a potentially powerful vector for anti-cancer agents.

Researchers in the UK working with viruses in the reovirus family found that they were able to cross the blood-brain barrier.   This discovery was made in a trial in nine patients who were scheduled to have surgery for hard-to-reach brain tumors.   The patients were given the reovirus, which was then found to have replicated in the brain tumors and triggered a influx of T-cells to attack the tumors.   The UK researchers are investigating a treatment regimen that would employ the reovirus in combination with other agents after surgery, to prevent recurrence of these difficult cancers.

In a similar experiment, researchers at Washington University / St Louis have used the Zika virus to target glioblastoma stem cells.   The Zika virus exhibits a preference for developing brain cells, but not mature brain cells.   This is why getting bitten by a mosquito that carries the Zika virus doesn’t do too much damage to adults, but does enormous damage to the developing brains of fetuses.   In mouse models of glioblastoma, the Zika virus, either alone or in combination with a chemotherapy drug, significantly slowed tumor growth and extended the lives of the little creatures, suggesting promise in treating glioblastoma in humans by this means.

An advantage of oncolytic viruses is that they are potentially inexpensive.   The viruses themselves may need to be genetically modified, but that’s a far cry from cancer therapies that rely on modifying the T-cells from each patient to target that specific patient’s cancer.   That doesn’t mean that when oncolytic virus therapies come on the market they will be cheap, since the research and development costs will certainly be high.

 Shedding some light on the so-called “obesity paradox” and BMI

For a start, the term “obesity paradox” is a misnomer, coined by Time magazine back in 2013 when a thorough meta-analysis examining the link between body mass index (BMI) and mortality was published in the Journal of the American Medical Association.   (Flegal KM, JAMA 2013;309(1):71-82)   The paper analyzed 97 studies and found that persons in the overweight category (BMI greater than 25.0) lived slightly longer that those in the normal category.   Time and other publications ignored the fact that while the overweight individuals had the best life-expectancy figures, those in the obese range (BMI greater than 30.0), along with those in the underweight range (BMI lower than 18.5), had markedly lower life expectancies.   So it’s not an “obesity paradox,” but an “overweight” paradox, which makes for a much less catchy headline.

That finding has never gone over very well with the health-care community, which generally continues to employ BMI values as a guide to individual patient management.   A group of researchers in Europe just published – last Friday, March 16, as I’m writing this – an analysis of nearly 300,000 participants in the UK biobank in which they found that the lowest incidence of cardiovascular disease events was in persons with BMIs around 22 or 23.   Lower and higher BMIs were associated with higher CVD events, although, as noted above, those differences were small.   (Iliodromiti S., EurHeartJ /ehy057)   However, those observations supposedly disposed of the “obesity paradox.”   To quote their conclusion,  “Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged.”

The outcome measure in the European study was not overall life expectancy, as in the JAMA study, but cardiovascular events – but let’s not split hairs.   Speaking more broadly, both studies found that there was a J-curve, in which a much higher incidence of the negative findings, whether death or cardiovascular events, were at the two end-slopes, which went up quite steeply from the gentler curve at the bottom.   In other words, the really high-risk groups were those with BMI values well below the 18.5 cut-point for underweight and well above the 30.0 cut-point for obese.   There was not much difference in cardiovascular events between the subjects clustered around the 25.0 cut-point between normal and overweight BMI values.

However, a basic question remains: should BMI, which takes into account only two body measurements, be employed in making life choices about any individual?   As surely you know, BMI is calculated on the basis of height and weight alone; an individual’s height is used as a surrogate for volume.   But this does not take into account what that volume consists of.   Our total weight is the sum of many subcategories – bone, muscle, fluids, waste, and, of course, fat.   The proportions of those vary immensely among the members of the human species.   Thus, individuals with identical BMIs can have widely differing ratios of fat to the other components of our bodies.

A study published in the International Journal of Obesity (Tomiyama AJ, Int J Obes (Lond) 2016;40:883-886) a couple of years ago should have scuttled the BMI as a meaningful indication of an individual’s health status.   Note, I’m perfectly willing to accept its usefulness on a population-wide basis; e.g., if the population of one state has an average BMI of 33 and that of another state an average BMI of 23, the people in that first state are likely to be at significantly higher risk.   But what that study made clear is that when it comes down to individuals, BMI is worthless.

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The researchers used NHANES (National Health and Nutrition Examination Survey) data to study the link between BMI and other health markers including blood pressure, blood glucose, insulin resistance, C-reactive protein, and cholesterol and lipid levels.   They found that about half of individuals in the BMI-overweight category were metabolically healthy, as well as 29% of people in the BMI-obese category.   Moreover, more than 30% of the supposedly normal-weight persons were unhealthy from a cardiometabolic perspective.   All in all, about 75 million people in the US are misclassified as being either metabolically healthy or unhealthy based on their BMI scores.

To quote one of the authors of the International Journal of Obesity Study, Jeffrey Hunger, “That should be the final nail in the coffin for BMI.”

Perhaps as a way to make the whole affair a bit more concrete, an NPR station did some digging around in the NFL’s data base and found that not one single player on the Denver Broncos had a BMI in the normal range.   All were either overweight or, Heaven forbid! – obese.

Being classified as overweight or obese according to the deeply flawed BMI criteria can have economic implications for a great many people.   The Equal Employment Opportunity Commission recently passed a rule that permits employers to increase what they charge employees for health insurance by as much as 30% based on their failure to “meet health criteria,” which can include BMI.

And BMI doesn’t appear to be going away.   A JAMA letter just announced that, according to NHANES data, 39.6% of American adults are obese, based on the BMI criterion.   It’s as though BMI is baked into the definition of “obese.”

A couple of bits of not-so-good news: number one, measles cases soar in Europe

The first of these probably does not directly affect most of the Gumshoe faithful, but it is certainly a cautionary tale.   To wit, according to the World Health Organization, the number of measles cases in Europe quadrupled in 2017, totaling 21,315, from 5,273 cases recorded in 2016.   At least 35 children died as a result of this occasionally deadly disease.   Most of these were in Romania, which accounted for 5,562 of the measles cases.   A factor contributing to the spread of the measles epidemic in Romania is that there is a large population of Roma people in that country, and they mostly do not vaccinate their children, nor seek prompt medical assistance when their children are ill.

The second highest total number of measles cases was in Italy, with 5,006 cases and three deaths.   The European Center for Prevention and Disease Control noted that 95% of the measles cases were in individuals who were unvaccinated or who had not completed the recommended schedule of doses.

It was noted that vaccination rate in Europe are lower than in the US.   There are a number of long-standing anti-vaccine movements in various European countries, and some conservative Protestant denominations believe that vaccination subverts God’s will.

In response, laws have been passed in France, Germany, and Italy requiring parents to have their children vaccinated, or at a minimum consult a physician about vaccination.   Italy and Germany have imposed fines ranging from $600 to $3,000 for failure to comply.

In the US, everyone born before 1957 is assumed to have had the measles as a child and is therefore immune, and the disease had been all but eliminated by about the year 2000, but travelers from other parts have brought the disease with them, and as a result there have been sporadic outbreaks of measles.   The Disneyland outbreak in 2015, which caused 150 cases, was thought to have been caused by infected travelers.   In response to the Disneyland outbreak, the state of California has outlawed exemptions from vaccination of schoolchildren based on “personal belief.”

This once again reinforces Doc Gumshoe’s preaching about herd immunity.   Yes, it is true that vaccination is not a 100% guarantee that you will not get the disease against which you have been vaccinated.   But if you and everyone with whom you have contact has been vaccinated, the odds that you will get that disease are very, very low.

Not-so-good news item: number two, decline in hip fractures levels off

From 2002 to 2015, a steady decline in the number of hip fractures sustained by women on Medicare over the age of 65 was recorded, from 931 per 100,000 in 2002 to 730 per 100,000 in 2015.   But over the past three years that decline has stopped.   If the reduction in the number of events had continued, it’s estimated that about 11,500 fewer women would have broken their hips.

Why has this happened?   The decline in hip fractures was attributed primarily to the introduction in 1995 of the drug Fosamax (alendronate), which, admittedly, was initially overprescribed to every patient in the very first stages of bone loss, termed osteopenia.   But a few years later there began to be reports of two adverse events related to bisphosphonates – fractures of the femur, and osteonecrosis of the jaw.   The first of these occurs very infrequently, and the second is extremely rare.

The current views of experts on avoiding fractures associated with bone loss does not call for treatment with bisphosphonates when the first signs of osteopenia become evident, unless other factors suggest that the patient is at a significantly increased risk of breaking a major bone.   Patients should be treated if bone density tests points to frank osteoporosis of the hip, spine, or forearm.   And, although patients who have already sustained a bone fracture should definitely be treated with a bisphosphonate, the great majority do not receive treatment.   This form of treatment has been definitively demonstrated to reduce the risk of a second bone fracture, but due to the fears related to the adverse events, very few patients agree to treatment, which declined from about 15% of patients in 2004 to just 3% in 2013.

The data points to a clear advantage for bisphosphonate treatment over non-treatment in appropriate patients.   The risk of fractures is far greater than the risk from the adverse events, but that doesn’t seem to induce patients to agree to treatment.   The narrative if familiar.   A new drug appears, and hopes go up that the condition it treats will diminish as a threat.   (My sagacious spouse recalls a friend telling her that with the introduction of Fosamax, women would no longer need to worry about osteoporosis.   She was dubious.)   Then, some scary side effects appear, and the current shifts.   Yesterday’s miracle drug becomes today’s health threat.

What Fosamax and the other bisphosphonates do is inhibit part of the process of bone remodeling, that being the term of art for replacing old bone tissue with new, stronger bone tissue.   But with age the two parts of the process can become unbalanced – osteoclasts, which remove old bone tissue, keep up their activity, while osteoblasts, which create new bone, slow down a good bit.   Therefore many people, especially post-menopausal women, lose bone mass, thus making them susceptible to fractures, which can lead to swift decline in all of life’s activities.   Bisphosphonates slow down the part of this remodeling process that removes the old bone.   They do not affect the bone-building activity of the osteoblasts, but their net effect is to prevent weakening of bones – old bone is better than no bone.   These drugs are valuable, despite their side effects, in a range of conditions, and – as with all forms of medical treatment – we need to consider carefully the balance between benefits and risks.

And, by the way, bisphosphonates are by no means the only drugs that treat osteoporosis.   Doc Gumshoe will follow up soon with a whole tract on the subject.

Some more cheerful bits of news

This one popped into my in-box with the intriguing title “Baking Soda May Reduce Premature Death Risk.”   If the Gumshoe faithful assume that my initial reaction was marked skepticism, that is correct.   It seemed to me akin to the frequent warnings that circulate in cyberspace, such as “Did you know that you have been brushing your teeth all wrong, and IT COULD KILL YOU!!!”   But the provenance of the baking soda piece does appear to be respectable, so here goes.

The data on which the baking soda / life expectancy association was based came from the Dynamics of Health, Aging, and Body Composition Study (HealthABC)  funded by the National Institute of Aging (NIA) and the National Institute of Diabetic and Digestive Kidney Diseases (NIDDK).   It followed a cohort of 2,287 generally healthy black and white older adults starting in 1997.   The mean age of participants at the start of the study was 76 years.   The general objective was to investigate the effect that changes in body composition have on functional decline in older persons.   Among many other data points, the blood gas measurements of participants were grouped into three categories based on sodium bicarbonate levels (baking soda is sodium bicarbonate, in case you forgot).   About 11% were found to have low bicarbonate levels and 10% had high bicarbonate levels.

Survival data on this cohort were collected through February 2014, for approximately 17 years.   The finding that led to the skepticism-provoking headline was that in the 11% group that had the lowest bicarbonate levels, mortality was 24% higher than in the group that had bicarbonate levels closer to the mean for the cohort.   The 10% that had the highest bicarbonate levels had a very slightly higher mortality – 3% – than those who were closer to the mean.   (Raphael KL, Clin J Am Soc Nephrol 2016;11(2)308-316)

Sodium bicarbonate helps the body in balancing pH levels (acid-base levels).   The study author, Dr Kalani Raphael pointed out that adding the pH measurement did not change the overall results.   The study notes that we don’t have to resort to putting spoonfuls of baking soda in our drinking water.   Eating more fruits and vegetables is the way to balance pH.   Apples, raisins, spinach, bananas, carrots, broccoli, lemons, and even coffee will boost our bicarbonate levels … and, we hope, keep us going longer.

But, wait just a minute – is it the increased bicarbonate blood levels, or it is eating all those fruits and vegetables that add to our life spans?   Yes, it might be that the bicarbonate is the driver of increased longevity, but it might also be that higher bicarbonate levels are just a side effect of the healthy diet, which is the real underlying cause of the added years of life.   As usual, there’s more work to be done.

Another optimistic note: a possible way forward in Alzheimer’s?

Doc Gumshoe is fully aware that there are many differences between human brains and mouse brains.   Mice, for example, are better at finding their way through mazes than we are, and have figured out ways of getting around and through spaces that would stump most humans.   We, on the other hand, have learned how to do really important things like play video games and exchange vital news with our BFFs on our devices while crossing the street in heavy traffic.   But there are enough areas of similarity between the murine and human brain to make the former a fruitful subject of study when combating Alzheimer’s disease (AD).

Researcher at Lancaster University in the UK have found that a treatment for type 2 diabetes (T2DM) seems to reverse memory loss in mice.   The treatment targets three growth factors that affect brain function – glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP).    Growth-factor signaling is impaired in individuals with AD.   When this form of triple therapy was administered to mice, it appeared to reverse memory loss, which was measured by means of a spatial water maze test.   Mice with a laboratory-induced model of AD termed APP/PS1 had previously performed well on this maze test but then appeared to forget how to navigate it.   But the drug improved their learning and memory formation, decreased the loss of nerve cells in the brain, reduced neuroinflammation (activated microglia and astrocytes) and oxidative stress in the cortex and hippocampus, and boosted the levels of synaptophysin, a growth factor that preserved the functioning of nerve cells.   And it also reduced the amount of amyloid plaque, one of the two abnormal brain growths that have been named as causative agents in AD.   (Tai J.   Brain Res 2018;1678;64-74)

The specific drug that targets those three receptors has not so far been named in the published research.   Thus far, liraglutide (Victoza, from Novo Nordisk), a widely-used drug for T2DM, has been investigated in small clinical trials in AD patients, with somewhat interesting results particularly with reference to a reduction in amyloid plaque.   However, liraglutide treatment resulted in no difference in cognitive ability between trial subjects.

The study authors modestly conclude that triple receptor agonists are a promising lead for the design of future treatment strategies for Alzheimer’s disease.

What I take from this is that these investigators were not pinning their hopes on the particular drug that they used in this study as a potential AD miracle cure.   The real value of the study was, in my opinion, to point the way to a better understanding of the physiologic mechanism that leads to AD.   The two big hypothetical “causes” of AD, being beta amyloid plaque and neurofibrillary tangles, both play some part in causing the dementia that characterizes the disease.   But attempts to pin most of the blame for AD dementia on either or both of them have failed.   It’s likely that both are contributors to AD, but that there are also other factors involved, and the total elucidation of the cause will be that a jumble of processes going on in the brain that essentially gum up the works.   These processes will likely have to be spotted and countered one at a time.   The study on the diabetes triple therapy may have identified some of them, and pointed the way to addressing them.

A disturbing trend

It concerns treating stroke victims with tissue plasminogen activator (TPA).   Until I read a piece in the Science Times, I assumed that TPA was the standard treatment for stroke victims if instituted in the first three or four hours.   TPA acts rapidly to break up the blood clot in the brain that causes the stroke.   The longer the delay before TPA is used, the more damage takes place in the brain – brain cells begin to die.   This causes a number of seriously disabling conditions in mind and body, and patients treated promptly with TPA are mostly spared.   It’s 22 years since TPA was introduced, and millions of stroke victims have derived huge benefit from that treatment.   How could it not be generally accepted?

However, it turns out that I was wrong.   There is a coterie of skeptics who maintain that TPA is dangerous, causing brain hemorrhaging, and that the studies supporting it are flawed.   Their view is that it’s better to let the stroke run its course.   These skeptics spread their views not through clinical studies in peer-reviewed journals, but through social media.   In spite of the strong endorsement of TPA treatment by both the American Heart Association and the American Stroke Association, some emergency physicians do not even offer their patients the choice of TPA, and some present the risk of brain hemorrhages as comparable to the risk of severe disability following a stroke.   The weight of the evidence refutes that view.   Severe disability resulting from a stroke is much, much more common that brain hemorrhage.   But when the risk is presented to stroke victims and/or their families, as many as half refuse treatment.

The TPA issue is similar to the shunning of bisphophonate treatment that I discussed earlier: the risk-benefit balance is distorted by people who place their thumbs heavily on the risk side of the balance, and therefore many individuals who could benefit from those options do not receive them.

The Science Times piece, by Gina Kolata, appeared on March 27th of this year in the NYTimes.   The headline is “A Stroke Treatment Mired in Controversy.”   [ed. note: the article was syndicated, and the headline is now different in some editions] I consider that headline to be far too even-handed.   I would have said something like “A Highly Effective Stroke Treatment Besmirched by Fake News.”

* * * * * * *

Before starting out on this installment, I wrote out a little list of the recent developments I wanted to cover.   I got to about half.   Is that because I run on too long about each item?   Never mind; I’ll try to get to some of the others before too long.   In the meantime, keep the comments, questions, and suggestions coming.

Best to all, Michael Jorrin (aka Doc Gumshoe)

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yukonjack
Member
yukonjack
March 29, 2018 4:12 pm

Assumptions are the mother of all disasters. I was born before 1957 and have never had the measles.

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Marco Polo
Marco Polo
March 29, 2018 8:02 pm

“Doc” just to clarify your response to yukonjack, are you implying that if he/she was born prior to 57 they likely had the vaccine, yet could still contract measles?
Or are you interpreting his assertion as he was born before 57 and may not have had the measles vaccination and somehow he is equating birth year to susceptibility to measles?
Color me confused.
I was born before 57 and had the “shot” so I assume measles isn’t something that I’ll contract even if exposed to a Disneyland troop of UN-vaccinated travelers.
Appreciate your point of view as youkonjack’s statement implies he may not have have the “shot” even though he was of that era.

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archives2001
archives2001
March 30, 2018 12:42 am

And don’t leave out Shingles…

jnsesq48
Irregular
March 29, 2018 8:18 pm
Reply to  yukonjack

Hey, when I was a kid waaaay back in the day, I had the (standard) trifecta: Mumps, measles and chicken pox. Hell, it made me the man I am today and… uhhh, never mind.

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backoffice
Irregular
March 30, 2018 3:05 am
Reply to  jnsesq48

I had all three also, I was born in 56. I’ve had all the shots also even the Polio vaccine.

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Lulu
March 29, 2018 10:49 pm
Reply to  yukonjack

yukonjack, I have never had the measles either, not any childhood disease, as mumps, measles, or chicken pox. Neither has my daughter who is 41 now and born without tonsils….that I always thought was weird.

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Rusty Brown in Canada
Member
Rusty Brown in Canada
March 30, 2018 2:03 am
Reply to  Lulu

I’ve been told the same a couple of times. I’ve never had a tonsillectomy, but I don’t have any apparent tonsils.

catmann
March 30, 2018 8:22 am
Reply to  yukonjack

Nor I but then… I ASSUME neither of us will ever have shingles either?

Dr. Hal
Member
Dr. Hal
March 29, 2018 4:36 pm

Fosamax… Seems to produce strong BRITTLE bones that break rather than flex under stress. Check out Dr. Frank Shallenberger’s Second Opinion Newsletter.com. He is an MD with a great track record for integrated health care. I am a retired Chiropractor and like most of what he writes.

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billyb
Guest
billyb
April 1, 2018 11:01 pm
Reply to  Dr. Hal

makes no sense unless you say strong, dense bone, or brittle, dense bone, because bone can not be strong and brittle at the same time by the definition of those terms.

seminole2
seminole2
March 29, 2018 5:09 pm

As someone who had multiple strokes due to a dissected artery, I can state that TPA can be very dangerous if the cause of the stroke is not fully understood. If TPA is given to a stoke patient who is experiencing a hemorrhagic stroke, the patient is as good as dead.

The sad fact is that even certified “Stroke Centers” often have antiquated CAT scan equipment that does not indicate a stroke or the cause of a stroke for 30+ minutes after the stroke occurs. The stroke specialist stated “congratulations, you did not have a stroke” just minutes before I experienced a second stroke.

TPA is a wonder drug when paired with a competent physician with state of the art equipment, but is deadly when a physician does not have the full details.

fizee
fizee
March 30, 2018 2:14 am
Reply to  seminole2

thank you seminole2 for sharing your experience. CVA (cardiovascular accident or stroke) can be due to haemorrhage (about 1/3 of incidence) or infarct (clot, about 2/3) and these are very different events although the effects are similar. As you point out, diagnosis is critical. The effects can be so serious and long term that it is really sad if treatment is with held due to fear based on ignorance, but treating a bleed as a clot is potentially disastrous. Response to a stroke needs to be fast but not rushed.

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Laura P. Schulman, M.D.
Laura P. Schulman, M.D.
March 29, 2018 5:55 pm

Serum bicarbonate levels in people who are otherwise in good homeostasis are a function of two things: the kidneys and the lungs. Ingested food has very little effect on the moment to moment level of measured bicarbonate. Your kidneys will sort out the big picture, and the depth and rate of your breathing will fine tune it. Don’t be fooled.

Gerry
March 29, 2018 6:59 pm

I agree, the acid base balance of the body is maintained at a very tight number any deviation is corrected by the action of the kidneys and lungs immediatly . Taking of acid or base orally will be countered by the body. Sodium bicarbonate was taken for many years by millions of people for gastric ulcers and acid reflux. It was the stable treatment for centuries.

archives2001
archives2001
March 30, 2018 12:58 am
Reply to  Gerry

OTOH, if the stomach does not produce enough HCL which many systems don’t as we get older, the result may be some aspect of putrefaction and intestinal disorder.
When most people complain about GERD or heart burn to their doctor, most will prescribe an antacid without even testing the patient for stomach acid. Talk about incompetent ‘Quacks’!

gummytree
gummytree
March 29, 2018 7:47 pm

Good to know Doc ! How about posting this on WebMD instead of this investment Site.

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gummytree
gummytree
March 29, 2018 7:34 pm

I do not mean to be impolite Travis but with all these current problems facing Investors struggling to keep up with falling Technology Stocks and recommendations (from you sometimes) but mostly from the likes of miriads of Scam Merchants like Matt Badiali ,Christ the Saviour of Cryptos – Ian King of Real Wealth Stratigist, James Altucher and Chicken Tikka Tiwarrrri- all big mouth babblers , 5 Min. Forecast, Winning Investor Daily, Sovereign Investor Daily …all promising to take your $2000+ subscription and giving FAKE PROMISES with only the Cop out Clause of “Obviously we cannot guarantee anything”………I am surprise that you seem to be running out of Topics to Elucidate and to give a better service to your Clients.
Your service is still the best …sometimes but compare to these Fake Merchants ?, well ….
I do not need a Medical Lecture that itself goes on and on and on – like the Fake Videos from the above Scam Folks reveling on the past successes of “put up” Clients. ( All of us can go back ,with hindsight, one or three years back to pick out Penny Stock Successes and post it on the Internet and then look like a successful Pundit and charge $$$$ for it or for a suggested “next big one” !

I told you some weeks ago that you look and sound Stale..come on- get with it Travis and do some good work for your Money…..Not the next Liquid Metal that takes hours to read….The Precis you afford to Irregulars would be perfect for all your Clients .You can then do some more work.

Your Knowledge is good to Middling at present …get with it and give us some PEPPER ! Figure out the Next big Crypto, the next big Marajuana Stock and
Secure Sectors to invest in – give some additional NEWS as to what is happening in the Investment World and YOUR thoughts and a little guidance ..do not be so afraid like the FAKE MERCHANTS. …I am aware that you make your daily Bread from these People but sometimes you have to stand up and say something !!!!

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Travis Johnson, Stock Gumshoe
March 29, 2018 7:46 pm
Reply to  gummytree

Thanks for the feedback.

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laa0709
March 30, 2018 11:28 am

Hi Travis
Very measured response to gummytree – very commendable. I perfectly understand that StockGumShoe is not a platform for spats (for that there is FB and others) but allow me to respond to him directly … this simply cannot be left unanswered.

pjwa
pjwa
March 29, 2018 11:10 pm
Reply to  gummytree

I hope, Gummytree, you will enlighten us about which drug you are taking. It seems to transport one to an alternative reality very effectively. Stock Gumshoe says a lot. He is certainly not stale, indeed is always alive to present issues being raised by newsletters, some of which have a scammy element, and some are trying to do a credible job.
Travis has a clear and successful process for cutting through the issues and grasping what is important. You, sir, are mistaken to come to this site for recommendations, rather you should aim to gain a better understanding .
I hope when you come back to earth, you can frame a few appropriate words to Travis.
Sincerely,
Patrick

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catmann
March 30, 2018 8:31 am
Reply to  gummytree

Dude…read his preface, we all need a DAY OFF once in a while!
Obviously, some of us more than others.
Besides, investment ideas can come from a myriad of sources. I for one have an elevated interest in biotech now so give it a rest…go out and play in the snow mebe.

frank_n_steyn
Irregular
March 30, 2018 10:41 am
Reply to  gummytree

I’m guessing this was intended as a humorous post, right?

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laa0709
March 30, 2018 11:28 am
Reply to  gummytree

gummytree, your post is beyond ridiculous and borders on being rude. What you do not seem to understand it is that Travis has never purported StockGumShoe to be a stock advisor service, although we do gain valuable insight into his investment strategies through insight into his own portfolio. If you want specific stock picks Google “top stock picks for 2018” which yields 7 million results which you can peruse at your leisure.

Your comments of inter-alia “you look and sound Stale”, “do some good work for your Money” & “Your Knowledge is good to Middling at present” are not only impolite but downright insulting.

The value of StockGumShoe is that it dissects very convincing and credulous punts from (mostly) unscrupulous money seeking pundits by first identifying the specific stock and then in detail (which btw most informed readers do appreciate) imparts the pertinent information on it. That is invaluable and can assure you it has resulted in saving many subscribers the wasted subscription fee to a newsletter which is more often than not often biased and published with ulterior motives (Please peruse https://www.stockgumshoe.com/2017/12/microblog-guru-ish-pundits-2/).

And do note that I am not blowing Travis’ trumpet, I live on the other side of the world and am merely a subscriber. I have over the years subscribed to most stock market newsletters out there and have found StockGumShoe to be one of the very few unbiased, informative and valuable publications. It has certainly saved me a lot of money, not only in useless subscriptions but also in reckless investments.

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catmann
March 30, 2018 11:41 am
Reply to  laa0709

Well said laao. You voice how most of the grateful readers here feel about this valuable site and all of Travis’s efforts to keep us enlightened.

sunny88
sunny88
April 5, 2018 11:24 pm
Reply to  laa0709

I second the motion re laa0709’s response. Indeed, Doc Gumshoe’s treatise and the various responses were not only enlightening, but may save lives.

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Slvrvet
Guest
Slvrvet
March 30, 2018 5:04 pm
Reply to  gummytree

I could not disagree more. Keep up the great job Travis

gunstar50
Irregular
March 30, 2018 7:49 pm
Reply to  gummytree

How dare you attack Travis. His integrity is unquestionable. He saves people thousands of dollars by not spending their hard earned money on most of these teaser scams. One of fifty may make people money. I will always back Travis 100% This is the best service anyone can ask for. So lucky I found it. Do your own DD. He gives us something to look at, and make up our own minds. Best money I have ever spent was joining Stock Gumshoe.

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Rusty Brown in Canada
Member
Rusty Brown in Canada
March 29, 2018 9:07 pm

The burning question to me is: when are they going to bio-engineer a variety of a virus or bacterium that eats artery plaque and nothing else. When there is no plaque left, it dies of starvation. Soon, I hope.

archives2001
archives2001
March 30, 2018 1:03 am

About the same time they come up with a self replicating bot, Rusty…”Be careful of what you ask for….” Recall HAL in the movie ‘2001’?

Farmerne
Farmerne
March 30, 2018 3:51 pm

Rusty
there is a treatment for artery plaque — it’s called Chelation -but the
established/old medical profession will not recognize it, – ’cause it’s the
side effect of the treatment for removal of heavy metals/

Walt in Colorado
Member
Walt in Colorado
April 4, 2018 3:16 pm

Not sure why we always think we need hi-tech solutions… There is excellent research showing that Vitamin K, taken as MK-7, does pull calcium from arteries and gets it back into the tissues where it belongs. I believe the therapeutic amount is around 300 mcg per day, split morning and evening. Co-factors needed are D3 (2000 – 5000 IUs/day) and Magnesium (400 mg. per day). These are all sadly deficient in our modern Western diet. What could be simpler?

But if you believe we become sick because we are deficient in non-natural pharmaceutical molecules, then all bets are off…

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johnpeds
March 29, 2018 11:00 pm

An excellent description of what’s going on, of the quagmire one can create when oversimplifying epidemiology studies and/or clinical trials. The research reports require careful reading even by their intended audience. They aren’t written for the general public and those that report on them for the public should do so responsibly. Too often a comment or relatively minor finding is exaggerated to fit a socio/politic view and the mass media, in it’s constant search for controversy seems always eager to publicize this manufactured controversy.
One has to feel for the “consumer”. Just what is a poor boy to do?
Of course I know your articles here are intended to help us invest wisely, not to make medical decisions so I truly hope you have other outlets for your comments and insights.

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backoffice
Irregular
March 30, 2018 3:13 am

Doc, what are your thoughts on the ph of drinking water? Is it better if it’s acidic or alkaline?

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billyb
Guest
billyb
April 1, 2018 11:10 pm
Reply to  backoffice

since blood is slightly alkaline (7.35-7.45), it is better than it be alkaline. Acidic beverages, including water, will chelate minerals and likely dispose of them through the urine. For this reason, alkaline spring water is better than a more acidic purified water.

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catmann
March 30, 2018 8:20 am

I find a good bit of humor in the timing of this article. Considering the announcement today of the new head of the V.A. and his tongue in cheek bemusing by SNL for his assessment of Trump’s ‘good genes’ as it relates to his BMI. Some of us, apparently, can function quite well on a diet of potato chips, big mac’s and virtually no exercize at all! Maybe we should study the health benefits of swinging all those various golf clubs?
With that said, it looks like deciding on permission for stroke treatment should be.considered BEFORE one has a stroke?
As to immunizations, I was really quite surprised that Califonie came down on their side. Especially when one considers how approving they are of so many other hair brained eyedeers. I personally feel it’s not the states place to decide on the health care a parent should give to their child agreeing instead with the states right to protect individuals who DO care for their community wellbeing by seeking out immunizarion. Parents choosing to endanger the community should have to suffer consiquinces such as isolation of their kids through home schooling and a national registration as is currently required of sex offenders. The state and the communities they serve are intitled to know about the people who pose a greater risk to the rest of the.community, so all the pare
nts can provide the level of protection they choose for their own children. Exercising one’s freedoms can be a tricky thing. Without any regulation whatsoever we are left to enforcing our own set of values on everyone else. A scary thought when you see the end result is a society with an alarming amount of violent deaths. I mean…how can one justify NOT immunizing their kids then sending them into a school with vertually no protection from deadly violence at all? I’d be currious to know if a child faces a greater threat to sever bodily harm when attending school from a hypodermic needle or a .223 round? I guess, until we defy the lobbyist and actually start some.studies on the problem we will just have to live with the speculations from the loudest and most verbose among us…and funerals.
“Have fun while you can. Fate is an aweful thing”, Youngbloods circa 1967…or…as Jim Morrison famously stated, “None of us gets out alive.” (About the same circa but that whole era is kinda…fuzzy for me now. Time to start adding some liraglutide to my daily dose of ice cold Porter?)

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bluechipholder
April 1, 2018 5:53 pm
Reply to  catmann

Would of been a better comment without the Trump remarks/slights.

catmann
April 2, 2018 10:41 am
Reply to  bluechipholder

I’m a retired little league umpire (still love the kids, couldn’t take the parental abuse), as such I’m compelled to ‘call um like I see um’.
To which I might add, anyone who is even remotely aware of what this administration is doing to our Republic and STILL takes offense at any perceived ‘slight’ again the president’s name I refuse to use then they are stupid. Unlike ignorance, stupidity is incurable and not nearly often enough terminal.
Wanting to avoid specific political attacks no matter how well deserved, I merely wanted to point out what I see as the obvious results of their irrisponsible and selfish policies.
You can be on either side of the 1.5 trillion dollar hand out to the richest people and corporations in America at the expense of the poorest and most needy among us BUT…the results of that single policy is GOING to have some VERY predictable results that have never in the history of humanity delivered on the contrived promises and out right LIES that brought them to fruition.
Evil is what evil does. When you’re knee deep in it and still can’t see it…it IS you.

Cleveland
April 2, 2018 1:54 pm
Reply to  catmann

Seems like you are saying the same thing over and over. Look in the mirror. “Evil is what evil does.”

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catmann
April 2, 2018 4:57 pm
Reply to  Cleveland

Sorry to distract you. Plz, go back to your Fox news feed, you might miss sumpin important.

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Mary Garon
Member
Mary Garon
March 30, 2018 6:21 pm

Regarding Fosamax, etc. Vivian Goldschmidt has a book and a protocol to follow that uses no drugs to reverse osteoporosis. ” SAVE OUR BONES” She advocates eating a diet of 80 percent alkaline foods. I loosely tried her protocol (which meant giving up my daily glass of milk (acidic). My bone density went from osteoporosis to osteopenia in a year. I used to be on Fosomax and would never take it again. Eating a mostly alkaline diet is very healthy also. Her website has so many reviews from people who were able to reverse their osteoporosis.

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tanglewood
March 30, 2018 11:29 pm
Reply to  Mary Garon
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LongOnLife
April 2, 2018 2:08 pm
Reply to  tanglewood

Looking at the list it is interesting that “low carb” foods are generally more acidic. If acidic is bad and alkaline is good, then low carb diets spell the end of us.

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Lee Nielsen
Lee Nielsen
April 1, 2018 8:29 am

See research at Paul H. Duray Pathology Research Fellowship that show borrelia burgdorferi aka Lyme disease spirochetes involved in multiple sclerosis, Alzheimer’s disease, Lewy body dementia. Lyme DNA found in amyloid plaques.

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Dresq99
Member
Dresq99
April 10, 2018 6:35 am

Hi Doc and Travis,

Another very nice review by Doc.

Would it be possible to either embed PubMed links, or include PubMed ID (PMID) numbers, when citing scientific journal articles? (For example, the Tai article in Brain Research is PMID: 29050859.) This would make it easier to access the original source material for those of us who are motivated to do so.

Thanks!

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