Cholera vaccine & Healthy Traveler bias?

[pjoshea13]

New update on the cholera vaccine topic from the Karolinska Institutet. Sweden, [1]

Cutting to the chase:

"We showed that administration of cholera vaccine after prostate cancer diagnosis is associated with a significant reduction in mortality (HR 0.46 ...) even after adjusting for all known confounders.

"However, the same effect (or even stronger) could be seen for several other traveling vaccines and malaria prophylaxis."

Uh-oh!

"Therefore, we conclude that this effect is most likely due to a healthy traveler bias"

As an avid reader of obituaries, I have noted that it is not uncommon for men to die while away from home. While on vacation or attending a conference, etc. I have not heretofore thought of travellers as a select group of healthy individuals.

Bottom line:

If you are well enough to travel, you have a lower risk of dying from PCa. LOL

{Perhaps only the very healthy consider going to places where a vaccine is considered necessary.}

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/356...

Vaccine

. 2022 May 21;S0264-410X(22)00611-9. doi: 10.1016/j.vaccine.2022.05.028. Online ahead of print.

Travel vaccines are strongly associated to reduced mortality in prostate cancer patients - a real effect or residual confounding?

Axel Möller 1 , Klaus Schwamborn 2 , Adrian Spillmann 3 , Janet Hoogstraate 4 , Robert Szulkin 5 , Olof Akre 6 , Lars Egevad 7 , Mark Clements 8 , Markus Aly 9

Affiliations collapse

Affiliations

1 Department of Urology, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Electronic address: [e-mail].

2 VALNEVA SE, 6, rue Alain Bombard, 44800 Saint-Herblain, Nantes, France. Electronic address: [e-mail].

3 VALNEVA AUSTRIA GMBH, Campus Vienna Biocenter 3, 1030 Vienna, Austria. Electronic address: [e-mail].

4 VALNEVA SWEDEN AB, SE-105 21 Stockholm, Sweden. Electronic address: [e-mail].

5 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden; SDS Life Science, Danderyd, Sweden. Electronic address: [e-mail].

6 Department of Urology, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Electronic address: [e-mail].

7 Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: [e-mail].

8 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden. Electronic address: [e-mail].

9 Department of Urology, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Electronic address: [e-mail].

PMID: 35610103 DOI: 10.1016/j.vaccine.2022.05.028

Abstract

Repurposing of existing drugs and vaccines for diseases that they were not originally intended for is a promising research field. Recently there has been evidence that oral cholera vaccine might be used in the treatment of inflammatory disease and some common cancers. Specifically, Ji et al showed that the administration of cholera vaccine after a prostate cancer diagnosis reduced prostate cancer specific mortality rates by almost 50%. In a cohort of men from Stockholm, Sweden, with more detailed cancer data and a higher coverage of exposure to vaccine, we replicated these findings using a marginal structural Cox model. We showed that administration of cholera vaccine after prostate cancer diagnosis is associated with a significant reduction in mortality (HR 0.46, 95% CI 0.31-0.69, p-value 0.0001) even after adjusting for all known confounders. However, the same effect (or even stronger) could be seen for several other traveling vaccines and malaria prophylaxis. Therefore, we conclude that this effect is most likely due to a healthy traveler bias and is an example of residual confounding.

Keywords: Cholera; Cholera Vaccine; Drug repurposing; Healthy traveler bias; Oral cholera vaccine; Prostate cancer; Travel vaccine; Vaccine repurposing.

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Teufelshunde]

What would the "malaria prophylaxis" they are referring to be? Any idea? Hydroxychloroquine?

[pjoshea13 in reply to Teufelshunde]

From the full text:

"It is interesting to note that Ji et al found no beneficial effect on malaria prophylaxis on prostate cancer mortality, whereas we found that it had quite a strong effect. In Sweden, Malarone (atovaquone/proguanil) (ATC code: P01BB51), mefloquine (ATC code: P01BA05 and P01BC02) and doxycycline are usually recommended for the prevention of malaria. However, doxycycline is normally used for the treatment of bacterial infection and is therefore not suitable to be included in this study, since it is not a traveling vaccine. Therefore, one possible reason for the different outcomes in our study is that Ji et al included doxycycline together with Malarone and mefloquine in their analysis (source: personal communication with the authors)." [2]

Doxycycline has been discussed before.

-Patrick

[2] sciencedirect.com/science/a...

[cigafred]

Patrick is becoming the Will Rogers of Healthunlocked.

[HopingForTheBest1]

Something to think about, but not readily available here nor actionable anytime soon. Expect it would take a lot of convincing evidence for any doctor to agree to administer.

[Hidden]

Does this prove beyond a shadow of a doubt that there is no advantage:"However, the same effect (or even stronger) could be seen for several other traveling vaccines and malaria prophylaxis. Therefore, we conclude that this effect is most likely due to a healthy traveler bias and is an example of residual confounding."

I've wondered how much the healthy user bias influences the results but their rationale seems simplistic. I could replace a word like this:

"However, the same effect (or even stronger) could be seen for several other anti-androgens. Therefore, we conclude that this effect is most likely due to a healthy user bias and is an example of residual confounding."

Given that "Men who are able to withstand ADT and anti-androgens are likely not on their deathbed and are healthy enough to use them and most of them are still hormone-sensitive"

Are there common links between various traveler vaccines?

[Graham49]

Patrick

They don't seem to have much evidence for this conclusion. They say they adjusted for all known confounders. Surely comorbidities and health (if known) should have been taken account of.

Anyway, is it possible to reduce mortality from prostate cancer by 50% by being healthy?

[pjoshea13 in reply to Graham49]

Graham,

I've told this story before, but maybe 16-17 years ago I was in contact with a man who ran a group on the West Coast. He told me that albumin was better than any PCa marker for determining if someone was going to be around in 5 years. That was based on observation. He was ahead of the curve. These days, it's recognized that subclinical inflammation has an effect on 5-year survival - even in people who are assumed to be healthy.

There are various ideas held in the group as to what "healthy" means, & many clearly believe that being healthy will prolong survival. I suppose that I am one of them.

-Patrick

[Justfor_ in reply to pjoshea13]

What can issue a bad albumin prognosis? Higher or lower the normal range?

[pjoshea13 in reply to Justfor_]

Low albumin in a seemingly healthy individual is generally due to subclinical inflammation. The "Modified Glasgow Prognostic Score" uses <3.5, but it's designed to spot hospital patients who are at risk for an unexpected catastrophic response to routine surgery.

My long-ago acquaintance used <4.0. Those guys in his group did not fare well.

My albumin prior to prostatectomy was 3.9. The usual polyphenols that men use against PCa are all nuclear factor-kappaB [NF-kB] inhibitors & therefore inhibit inflammation. I was quickly able to get albumin to 4.5, which I think is a reasonable target.

-Patrick

[Justfor_ in reply to pjoshea13]

Thanks Patrick. My albumin post RP has been on average 4.51 (4.36 - 4.70). Considering your long-ago acquaintance's rule of thumb, HU members will have to endulge me for the next 5 years. Poor souls!

[Schwah in reply to pjoshea13]

Isn’t CRP also a good marker for inflammation and thus a good predictor of future health?

Schwah

[pjoshea13 in reply to Schwah]

There are a number of markers for inflammation - for instance: high neutrophils and low lymphocytes together (the NLR - neutrophils:lymphocytes ratio has often been used to predict who will respond poorly to a PCa drug.).

The Modified Glasgow Prognostic Score combines albumin & CRP.

A CRP of zero, as Nalakrats has had, would certainly be comforting.

-Patrick

[dhccpa in reply to pjoshea13]

Isn't there a ratio that uses C Reactive Protein? Maybe the one with albumin you mentioned. But I've forgotten how that ratio works.

[Ralph1966]

I read somewhere that the Cholera vaccine should be taken within 1-2 years of PCa diagnosis/treatment? Otherwise, it will not be helpful?

[Spyder54]

Thanks Patrick. I guess TA is referring to the “healthy traveler bias” as a confounder in the study?“We showed that administration of cholera vaccine after prostate cancer diagnosis is associated with a significant reduction in mortality (HR 0.46, 95% CI 0.31-0.69, p-value 0.0001) even after adjusting for all known confounders. However, the same effect (or even stronger) could be seen for several other traveling vaccines and malaria prophylaxis. Therefore, we conclude that this effect is most likely due to a healthy traveler bias and is an example of residual confounding.”

[pjoshea13 in reply to Spyder54]

Yes - I played into his hands with my post.

I feel that it is important to report all studies of interest, not just those that support my own bias. The Karolinska team did not prove that the cholera vaccine was of no value, but they did cast doubt. I'm surprised that someone who dismisses almost every paper posted by someone else, would accept the finding of "healthy traveler bias". What the heck is a "healthy traveler" (versus the presumably less healthy non-traveler)? Not a lot of non-travelers will take a traveler vaccine - except in this group, perhaps - although Americans do have to travel to Canada to get the cholera vaccine.

In a related post, Nalakrats pointed out that there are numerous studies that support the use of Metformin - so why the cherry-picking? Because if it's not SOC, all hope for benefit must be quashed.

Best, -Patrick

[MateoBeach]

Oh darn. Cat’s out of the bag. Spoiled it! Maybe that is why Dukoral is more effective for those in the USA. Have to travel to Canada to get it. (Not like going to Haiti though.)

[George71]

I went to Toronto about 3 years ago to get Dukoral after the first report on it came out I brought back a second dose in a carry on bag with ice from an airport concession stand (and took it about a year and a half later) ..... as I recall the original study was comparing PCa patients who had taken Dukoral to PCa patients who did not. I think you can order Dukoral online and have it shipped from Canada.

I wonder what someone on here would say about the recent study citing the nearly 2 fold increase in heart problems due to Aber. and Extandi ---

"commonly used PCa meds less safe than originally thought."

news-medical.net/news/20220...

medicalxpress.com/news/2022...

[GeorgeGlass in reply to George71]

Great point!

[CAMPSOUPS in reply to George71]

I wonder what someone on here would say about the recent study citing the nearly 2 fold increase in heart problems due to Aber. and Extandi ---

"commonly used PCa meds less safe than originally thought."

I could be wrong so no offense if taken but I feel like you presented this as if it is/was a secret that was kept from patients.

I am glad that as is standard continual statistical information, Dr. interviews and surveys took place since Zytiga and Xtandi were put out into clinical use. This is how the medical community continually adapts to real world information to address dangers and concerns that come up with any drugs on the market.

These drugs are life savers and as with many life saving drugs including chemo, Ra-223, Lu-177, radiation, surgery, etc. the patients must be closely monitored and again fortunately that monitoring data is also collected and a issuance of revelations such as in the articles you linked to is passed thru the medical community to cause an emphasis in patient monitoring for the possible side effect events mentioned.

Please don't take my Zytiga away (lol) unless it is found it is going to out right kill me lol.

Since starting Zytiga a year ago my medical team has had monthly blood draws to monitor liver function and cardio tests every 6 months even though I never had a history of trouble with either so even before the official medical analysis as noted in the links you offered it appears that even by word of mouth these possible side effects were discussed within the medical/scientific community. Now with the information formerly disseminated all patients on Zytiga will be closely monitored.

[CAMPSOUPS in reply to CAMPSOUPS]

ncbi.nlm.nih.gov/pmc/articl... Nothing devious about the knowledge of risk of hypertension and afib with use of abiraterone.

[GeorgeGlass]

I know several elderly men who are currently in really bad condition, and a couple who died, following vacations on cruise ship vacations trip to Costa Rica, cv19 vaccine etc. If your immune system is weak and you go to locations where there are viruses, bacteria that your body has not been exposed to in several decades, then you are going to have a difficult time fighting off those foreign invaders.

[j-o-h-n]

The ice is the secret...........

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 05/26/2022 11:13 PM DST