June 13, 2024 • 35 mins
Can drinking milk potentially increase your risk of breast cancer? Join us as we explore the controversial link between bovine leukemia virus (BLV) in milk and breast cancer risk. Sparked by a patient’s concern and a meta-analysis review, this episode emphasizes the importance of asking detailed questions in understanding scientific research.
We critically examine a meta-analysis on BLV and breast cancer, uncovering significant methodological flaws, from lack of pre-registration to biased selection criteria. Our discussion highlights the need for intellectual honesty and rigorous scrutiny in healthcare research.
We also question the credibility of the systematic review, pointing out the drastic reduction of eligible studies and the peer review process's legitimacy. By discussing the 2.57 odds ratio of BLV's association with breast cancer and the difference between correlation and causation, we aim to provide a comprehensive understanding of the challenges in interpreting scientific research. Tune in to gain insights into the complexities of medical studies and the importance of critical appraisal in healthcare.
Learn more and become a member at www.DrJournalClub.com
Check out our complete offerings of NANCEAC-approved Continuing Education Courses.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Introducer (00:02):
Welcome to the Dr Journal Club podcast, the show
that goes under the hood ofevidence-based integrative
medicine.
We review recent researcharticles, interview
evidence-based medicine thoughtleaders and discuss the
challenges and opportunities ofintegrating evidence-based and
integrative medicine.
Continue your learning afterthe show at www.
(00:23):
d rjournalclub.
com.
Dr. Joshua Goldenberg (00:31):
Please bear in mind that this is for
educational and entertainmentpurposes o nly.
Talk to your doctor beforemaking any medical decisions,
changes, etc.
Everything we're talking aboutthat's to teach you guys stuff
and have fun.
We are not your doctors.
Also, we would love to answeryour specific questions on
drjournalclub.
com.
You can post questions andcomments for specific videos,
(00:55):
but go ahead and email usdirectly at josh at
drjournalclub.
com.
That's josh at drjournalclub.
com.
Send us your listener questionsand we will discuss it on our
pod.
Hello, this is Dr JoshuaGoldenberg and Dr Adam Sadowski
and we are here for take 17 oftoday's episode, where we are
(01:19):
desperately trying to beattechnology and the technology
gremlins which is a thing andactually record this stinking
podcast.
So, as I was saying before,Adam, this article that we're
talking about today was broughtto my attention by a patient of
mine who said hey, josh, wouldyou mind reviewing this meta
(01:39):
analysis?
And I just had this likeamazing moment, like I don't
think a patient has ever askedme to review a meta-analysis.
You just warmed my heart andthen I proceeded to completely
forget about it.
She like very kindly remindedme when I saw her the other day.
So, um, this is my attempt tomake amends and actually review
the article.
She had questions about uh,bovine, what is it bovine
(02:03):
something virus?
What is it bovine?
Bovine, what is it Bovinesomething virus?
What is it Bovine?
Dr. Adam Sadowski (02:06):
Bovine leukemia virus.
Dr. Joshua Goldenberg (02:08):
Leukemia virus.
Dr. Adam Sadowski (02:10):
And before we get into the episode, if
listeners, if you do send usstuff, do a one over and kind of
like, ask us what the questionis that you're looking for.
Don't just say is this a goodpaper, like is this good?
Because that's a relative termand we're not giving any medical
advice on this podcast either.
(02:31):
So if you have a paper, do likewho was it that sent in a paper
and had like six pinpointquestions to ask about it.
Dr. Joshua Goldenberg (02:41):
Was it Mark Mark Davis?
Dr. Adam Sadowski (02:43):
No, it wasn't .
It wasn't Mark Davis, it was,oh my gosh, dr Yarnell.
When Dr Yarnell did that, thatwas helpful because we knew sort
of like what we, what theintent of the paper was, outside
of our own interest.
So if you send us a paper, readit and give us your input and
give us a question.
If you don't know what you'rereading, go Dr.
(03:06):
Journal Club.
Dr. Joshua Goldenberg (03:08):
So let me give some background, because
in this case the patient gave melots of background information.
So, basically, I think she hadheard about this bovine leukemia
virus in the supply of milk andthat I think there were a
couple European countries Ithink she was saying that had
like gotten control of the virusin the bovine population
(03:28):
because there was this supposedconnection with breast cancer
and so she was concerned.
She wasn't sure if she wouldshould continue to drink milk or
not, or if it would be I thinkshe was traveling and if it
would be okay to have the milkin these countries.
So that was the question.
So very targeted question havethe milk in these countries?
So that was the question, sovery targeted question.
(03:48):
And then what I was excitedabout is you know, someone you
know, coming up with an actualmeta-analysis and knowing what
that was and be like, hey, whatdo you think?
So let's jump into it.
So let's see here, all right.
So, oh, of course, because thisis how this day is going, my
PDF player is off.
Dr. Adam Sadowski (04:05):
Well, that's okay, I've got it.
Dr. Joshua Goldenberg (04:07):
Oh, you got it.
Okay, great, why don't you setus?
You want to set us up with somebackground in methods and then
we can do like a critical evaland take home Keep it a little
short today, Sure sure, sure,sure.
Dr. Adam Sadowski (04:19):
So basically, what this study is looking at
is trying to look at some sortof association between this
virus known as bovine leukemiavirus, which I had never heard
of.
Dr. Joshua Goldenberg (04:29):
Me neither.
Dr. Adam Sadowski (04:30):
And the risk of breast cancer.
Dr. Joshua Goldenberg (04:32):
Oh, sorry , sorry, that reminds me, this
is what it was.
She had asked me about this andI said I have no idea.
So what does she do?
Because she's amazing, shecomes back with a freaking meta
analysis and asked me to thenopine, that's so awesome, right?
So anyway, yeah, go ahead.
So now I'm remembering.
Dr. Adam Sadowski (04:49):
Now it's all coming back, go ahead, yeah,
yeah, yeah.
And so this was a systematicreview and meta-analysis of case
control studies.
And so, for those who don'tknow what a case control study
is is you're taking cases andcontrols.
So there's the there.
Dr. Joshua Goldenberg (05:05):
So in this case, with breast cancer
and without breast cancer.
Dr. Adam Sadowski (05:09):
Yes, and so in a case control study, you
have cases and you have controls.
The controls are individualswho would not have some sort of
exposure or, excuse me, somesort of outcome of interest.
And these are, and you'recomparing them to cases, and
they're called cases becausethey already have the outcome of
(05:30):
interest that you're interestedin.
So in this case, the case wouldbe breast cancer and they're
taking people who have breastcancer already diagnosed and
comparing them to a group ofcontrols who, in theory, outside
of the breast cancer diagnosis,are very similar in their
(05:52):
demographic makeup, if you will,relative to the individuals
with breast cancer.
So you're trying your best tosay, hey, we have these two
groups of individuals.
You're trying your best to say,hey, we have these two groups
of individuals where the onlydifference is that one has
breast cancer and one doesn't.
(06:13):
Now, in reality, that's not.
That's not the case, becausethese are, these are, you know,
sort of low, low levelobservational studies.
So you know that there aregoing to be a lot of differences
, going to be a lot ofdifferences, and that's why we
like randomization is because ifyou're randomizing participants
to two different groups,there's basically a nice
evenness, if you will, betweenthe two groups.
If there's any sort ofdifferences, so those
(06:34):
differences get accounted for,whereas with this they don't.
Dr. Joshua Goldenberg (06:37):
Right and so, and there's some cases
where I mean can't randomize toget breast cancer.
Dr. Adam Sadowski (06:41):
So it's like like it's usually these harm
studies like this where you'relooking at these case control
studies because obviously youcan't randomize to that same
with like smoking sensation,stuff like that or you have a
very rare outcome where, yeah,you would have to recruit
millions of people just to getone outcome, or you would have
(07:02):
to get several thousand peopleand watch them, for you know 30
years before you get one outcome, or you would have to get
several thousand people andwatch them for you know, 30
years before you get one event.
And so it's just from apractical standpoint doesn't
make sense to do that.
So this is if you already havethe cases, you can kind of
compare them to the control, soit's kind of the next next best
option.
And then you look backwards intime and kind of look, for you
(07:25):
know, were they exposed tosomething or not?
And then, if they were, isthere an association between
that exposure and the outcome?
So in this instance we have ourcases which are individuals
with breast cancer, and then wehave our control people without
breast cancer and we're lookingback in time to see if people
(07:47):
who are exposed to the bovineleukemia virus had a greater
odds or greater likelihood ofdeveloping the outcome of
interest.
So in this case, breast cancer.
Dr. Joshua Goldenberg (08:00):
Well, so opposite in this case, right?
So it's like of those withbreast cancer.
Do they have an increased oddsof testing positive on this
virus test, right.
Dr. Adam Sadowski (08:09):
Okay, and so, to kind of set this all up,
they basically said that youknow, breast cancer is very
common.
I think our listeners are awareof that.
I don't think there's anythingyou know from that that we
really have to talk on, to talkon.
(08:29):
However, with regards to thebovine leukemia virus, basically
it belongs to a family of virusknown as retroviridae, so
they're retroviruses, and thenthere's different classes within
that and then the main hostwhere we would find them is in
cattle, but they can be in otheranimals as well.
And I thought it was funny thatthey said that the prevalence
of the virus infection is highin cattle and varies anywhere
(08:51):
from 39 to 100%.
Dr. Joshua Goldenberg (08:54):
That was mind-blowing yeah.
Dr. Adam Sadowski (08:56):
Yeah, so basically half or all cattle
have this virus.
Dr. Joshua Goldenberg (08:59):
Yeah.
Dr. Adam Sadowski (09:00):
And it can easily transmit through infected
blood and milk.
However, it causes disease inless than 5% of infected cattle.
So I mean, if you kind of thinkabout it, it's kind of like H
pylori in humans, where allhumans basically have H pylori.
The issue is when it causesdisease disease?
Dr. Joshua Goldenberg (09:27):
yeah, and then did you get a sense of
like is it only infectious tohumans if the cattle is actively
showing disease, or or if theyhave it right?
Um, I don't, that wasn't clearto me because it's like oh my
gosh, like I like a half to allof beef have it, or dairy have
it, and I don't know how that'sjust not being passed all the
time.
But but I guess if you'resaying only 5% are infected or
show disease, rather I supposethat's when you would be more
(09:49):
likely to spread the disease.
But it seemed like they weren'treally clear on how infection
to humans happened.
Dr. Adam Sadowski (09:55):
Well, they also said that the mechanism of
transmission to humans is notknown, with the exception that
raw milk consumption cantransmit the virus from cattle
to human population.
Dr. Joshua Goldenberg (10:06):
Right, so you got to watch the raw milk.
Did I ever tell you my raw milkstory Super fast?
So, okay, really really quick.
Dr. Adam Sadowski (10:13):
On the topic of tangents.
Dr. Joshua Goldenberg (10:15):
Yeah, no, I know, I know, Hold on.
You got to let me have this onebecause as I was reading it I
remembered it and I hadn'tremembered it since, like I
don't know, over a decade ago.
Anyway, long story short, in mywandering years I was
backpacking through CentralAmerica and I was living in
Guatemala for like a while and Iwas living with a Guatemala
Teca family and the mother wassort of like the surrogate
mother while I was there and itwas, like you know, didn't
(10:39):
really speak much English and itwas super fun.
Anyway, she was really into farout there natural things.
She was doing like these, likenaturally, essentially
naturopathic stuff, but out inlike the mountains of Guatemala,
and one morning she's like Josh, I have to take you, I have to
show you something.
So we hiked all the way up intothe mountains outside of town.
We were in a town called Sheilaand we go up and we just stop
(11:09):
at this like random farm, justwhips out a.
Um, we're on a hike and it'slike she's thirsty.
So she whips out her cup, walks, knocks on the on the farmer's
door, he comes out, he grabs thecup and he sits down in front
of the cow and just startsmilking it directly into the cup
and she's just down the hatchand off we go and we're on our
we're on the rest of our hike tosome like amazing, like sweat
(11:30):
lodge up in the mountains orsomething.
Anyway, that was.
That's my raw milk story.
Dr. Adam Sadowski (11:33):
My raw milk story is that, uh, the farm that
my dad grew up on, uh, is still.
They still own it and it's justone of his brother brothers
operates it and when I went togo visit we just, you know, we
put milk in a bucket and we justhad it from there and then,
like the next day, if you wantedmilk or something like you,
just open the fridge and so coolit was just literally farm
(11:56):
fresh milk, but yeah, notpasteurized or anything.
Dr. Joshua Goldenberg (11:59):
That is so cool.
Yeah, well, as far as we know,you don't have bovine leukemia
virus, although I guess we don'tknow for sure, it's always a
possibility.
Anyway, I love those stories.
Okay, so what we're talkingabout?
Oh yeah, tangents.
All right, so back we go totalk about the study and all
right.
So I think that's enough formechanism.
(12:19):
They were pretty.
The authors themselves werepretty light on details of how
this could work, except thatbasically saying, yeah, cancers
sometimes are associated withviruses.
We've got multiple examples ofthat.
There's evidence that breastcancer maybe 10, 20% of it may
be associated with differentviruses.
What about this one?
There's been multiple studies.
Let's meta-analyze it.
That was sort of like the setupas far as I could tell.
(12:40):
Anything else you want to addfor the setup?
Dr. Adam Sadowski (12:42):
No, that's it Okay, far as I could tell.
Anything else you want to addfor the setup?
No, that's it Okay.
Should we jump into methods andcritique thereof?
Yeah, so basically what theydid is they followed the PRISMA
reporting guidelines, which inall honesty, doesn't really mean
much.
And then what they did was allcase control studies that
investigated the virus infectionand breast cancers were
collected from several databases, and then that's kind of like
(13:08):
how they picked studies,eligibility criteria, looked at
case control and prevalencestudies in English between 1995
to January of 2020.
And then detection of the viruswas through random assays and
then they were excluded if theywere published in languages
(13:31):
other than English.
Studies other than breastcancer or other viruses that
were not bovine leukemia virusinfection in any sort of male
participants, and they also didnot include other systematic
reviews or meta-analyses, whichI thought was kind of an issue,
because there are ways where youcan kind of use that data.
Dr. Joshua Goldenberg (13:53):
They said .
They seemed to suggest no onehad done it before.
I don't know, maybe I misreadthat, but that's fine, Then then
.
Dr. Adam Sadowski (13:59):
okay, then I'll give them a pass.
Dr. Joshua Goldenberg (14:00):
But how would they know that?
If yes, how would they knowthat if?
Uh, I guess how would they knowthat if they hadn't done a
search?
So, to your point, just trustus, just just yeah.
Well, I think that just trustus is kind of throughout.
So there's no registration thatI can see.
Dr. Adam Sadowski (14:17):
Did you catch a registration?
No, I didn't see one yeah, sothey didn't register.
Dr. Joshua Goldenberg (14:20):
So if we think about like, okay, so, so
that's basically the method,just like you said, so if we
quickly go through the sevendeadly sins, so remember the
seven deadly sins for systematicreviews, so we've got.
Did they register Ideally apriori?
No, did they do.
Was their search quality decent?
Did they explain?
Dr. Adam Sadowski (14:37):
They didn't expand upon that.
Dr. Joshua Goldenberg (14:39):
Yeah, well, let's go through all these
.
Did they give rationale fortheir exclusion?
Did they do a risk of biasassessment?
Did they do adequatemeta-analytic methods?
Did they see how the risk ofbias impacted their
meta-analytic result?
And was there publication bias?
So these are the seven deadlysins.
These are the critical domainsof AMSTAR II.
If you have any one of these,be off.
(15:05):
Your entire systematic reviewis considered critically flawed
and you cannot rely on it at all.
Look, the thing is we don't dothis for money.
This is pro bono and, quitehonestly, the mothership kind of
ekes it out every month or so,right?
So we do this because we careabout this, we think it's
important, we think thatintegrating evidence-based
medicine and integrativemedicine is essential and there
(15:28):
just aren't other resources outthere.
The moment we find somethingthat does it better, we'll
probably drop it.
We're busy folks, but right nowthis is what's out there.
Unfortunately, that's it, andso we're going to keep on
fighting that good fight and ifyou believe in that, if you
believe in intellectual honestyin the profession and
integrative medicine and beingan integrative provider and
bringing that into theintegrative space, please help
(15:51):
us, and you can help us bybecoming a member on Dr Journal
Club.
If you're in need of continuingeducation credits, take our
NANSEAC approved courses.
We have ethics courses,pharmacy courses, general
courses.
Interact with us on socialmedia, listen to the podcast,
rate our podcast, tell yourfriends.
These are all ways that you cansort of help support the cause.
Help support the cause, solet's go through here.
(16:19):
So first, deadly sinregistration.
We both saw no evidence ofregistration, so we don't know
if they came up with theirmethods after the fact.
And that's of course, a problemwhen you're looking at outcomes
and you basically say, well,you're just reporting the stuff
that looks sexy, especially whenthere are some interesting
calls about their methodologies,which I think there there were
some.
So that's number one.
So already we've got one deadlyflaw search quality.
(16:41):
What do you think about thesearch quality?
They didn't really go into it.
Yeah, they didn't.
That's a problem.
Yeah, so there's no, thereshould be a in an abstract or
something, at the very least thepubmed search strategy.
There was not.
They gave a couple, a handfulof like mesh terms that they
basically riffed on, but that'sabout it.
(17:03):
Um, also, they said verystrange things.
I don't know if you caught this.
They said that theyindependently did the search,
which makes zero sense.
Dr. Adam Sadowski (17:10):
You don't independently do the search, you
independently screen the searchit may be a translation issue,
because this was, I think, basedin Iran.
Yes, yes, and so they may haveyou know.
It may just kind of be likeloosely translated incorrectly.
Dr. Joshua Goldenberg (17:27):
I think we give them that one.
I think you're probably rightabout that, because it would
just be so bizarre to do that.
That.
I think you're probably right.
Okay, so we'll give them a passon that.
But they don't really reporttheir search really at all.
I don't like that.
They only included studies inEnglish.
I don't think that makes anysense.
Why would you do that?
And I think you might beopening yourself up for bias.
So I would say concerns,critical concerns.
(17:51):
I don't know, probably, if youwanted to be strict about it,
but I didn't like the searchvery much.
Next, one exclusion rationaleDid you see anywhere a list of
studies they excluded on a studylevel that explained why for
each study?
Nope, nope, I didn't see it.
Either they did aggregate stuff, like we excluded eight for you
know they didn't have this orthey didn't have that, but there
(18:12):
is no individual study levelwhere you could go and say so.
We got another critical flawthere.
Did they do risk of biasassessment on the primary
studies?
Dr. Adam Sadowski (18:21):
Kind of.
Dr. Joshua Goldenberg (18:22):
They did, yeah, they did.
Was it Newcastle, Ottawa?
I think they used.
Dr. Adam Sadowski (18:26):
Well, so that's not necessarily.
Well, actually, yeah, that is arisk of bias tool, because they
had it as quality assessmentand so those two are different.
I view quality assessment assomething like a grade, whereas
this really should be a biasassessment which can then
influence the quality.
Dr. Joshua Goldenberg (18:47):
Yeah, and like you said earlier, language
matters.
I 100% agree with you.
I think, unfortunately, peopleare loosey-goosey with this
language and you see that a lotthey talk about study quality
when really what they mean isrisk of bias, to your point.
Maybe it's a translation thingtoo.
But yeah, so they did do a riskof bias assessment.
They only included studies thatscored high, like that did well
(19:12):
on the risk of bias assessment,which I thought was interesting
.
It was like sort of a strictinterpretation.
They had a threshold cutoff andthey said we only are basically
looking at the studies abovethis.
It threw me a bit, becausecalls like that it's like why
and when did you decide to dothat, and I would be much more
comfortable.
Dr. Adam Sadowski (19:32):
And why that score?
It seems arbitrary.
Dr. Joshua Goldenberg (19:35):
And why that score?
Yeah, is that standard?
Is that considered a standardhigh level?
And again, like if we had a apriori registration, we'd say,
oh yeah, this is what they planto do.
They were worried about risk ofbias studies, but we just have
to, kind of like you said, taketheir word for it now.
So I give them a pass on therisk of bias assessment, but I'm
a little questioning abouttheir inclusion.
Dr. Adam Sadowski (19:57):
What I would have done, too, was I would have
included all of them and then,if you wanted to do like a
sensitivity analysis, say, okay,we're only going to include
studies with a score of, let'ssay, four or higher.
Yes, and we're saying four orhigher because and then have
(20:17):
evidence saying why, why thatnumber, as opposed to just an
arbitrary number, saying, oh,this, this sounds like it's a
higher quality.
Dr. Joshua Goldenberg (20:24):
Yeah, that's the right way to do it,
in my opinion.
You, you have all the evidenceand then, exactly, you view risk
of bias as a sensitivityapproach.
So I agree with you on that one.
I have seen other people dothis.
I agree with you though.
But yeah, and then I think theymeta-analyzed appropriately.
I didn't see any technicalproblems there.
The risk of bias impact ontheir overall estimate is kind
(20:47):
of moot, because they onlylooked at low risk of bias
studies and then publicationbias.
They did visual inspection andstatistical analyses, which is
appropriate, but the rule ofthumb for publication bias is
you don't do those if you've gotunder 10 studies, and they only
meta-analyze nine.
So it's underpowered.
(21:09):
So for them to say we didn'tsee any evidence of publication
bias, I mean it doesn't reallymean anything.
It's an underpowered test atthat point.
Dr. Adam Sadowski (21:27):
No one's going to see evidence of
publication bias.
So I don't know, I don't know amethodologist on their team,
yeah, and just kind of used sortof like very rudimentary
methods to this.
Dr. Joshua Goldenberg (21:39):
Yeah, I agree.
So I think my take home isthey've got three, three and a
half critical flaws.
This is a critically flawedsystematic review.
We'll talk about the results ina second, but pretty much I
don't trust the results beforewe even kind of talk about them.
Is my take home on that one?
Anything else on methods youwant to add?
Dr. Adam Sadowski (21:59):
No, that's it .
Dr. Joshua Goldenberg (22:00):
OK, cool, and I think you had the same
impression, sort of talking inthe green room there as well.
Ok, so let's talk about results.
So both of us are skepticalabout what the results will be,
but we'll.
Oh, they also had like crazyheterogeneity 80, not crazy, but
very high, 85 percent 85percent yeah, yeah, super
(22:24):
heterogeneous.
Um, they tried to exploreheterogeneity but I don't see
that they talk about.
Did I miss the results of theof the subgroup analyses?
Dr. Adam Sadowski (22:36):
nope, but.
But I think what we should sayis that they apparently they
started off with 13 000 studiesoh yeah oh right, so they start
off with 13 000 studies, andthen, of 70 that that remained,
uh 61 were included, and sothat's how they got to nine.
Honestly, I'm very skepticalthat their search strategy had
(22:58):
any sort of relevancy.
It's probably 13,631.
Dr. Joshua Goldenberg (23:03):
It makes no sense.
Dr. Adam Sadowski (23:03):
Probably picked up anything that had
bovine leukemia virus in thetitle, so it could have been
like you know BLV and rats.
It probably was not a goodsearch study.
Dr. Joshua Goldenberg (23:11):
You know BLV and rats it probably was not
a good search study.
So your point is the uppernumbers really high, so it
wasn't a very specific search.
Like I agree, you're probablyright and with everything else
we see, I don't know that wegive them a pass to say, oh,
they were trying to be overlysensitive.
But look at the next thing inthe Prisma flow chart.
So it goes from 13,608 to afterremoving duplicates and quote
(23:35):
irrelevant material or whatever70.
70.
What?
What does that mean?
So you remove duplicates?
Maybe I don't know.
You remove 1,000, 2,000.
So there's still probably, likeI don't know, 10,000 studies
and then they remove irrelevant.
Who's removing irrelevant?
Based on what right that soundslike?
(23:56):
I don't know.
Is that?
Do they mean title and abstract?
But no, they don't, becausethen they take of those 70, 20,
they only are screening 20 ontitle and abstract.
Like just to give peoplecontext, like we will often
screen thousands on title andabstract and somehow they get to
20 by quote removing irrelevantstudies in some mysterious way.
(24:17):
I don't know what that means.
Removing irrelevant studies?
It is the biggest red flag I'veever seen on a Prisma flowchart
.
I don't know how this passedpeer review.
Maybe this is not a legitjournal, I don't even know,
maybe it's one of thesepredatory journals.
This is just beyond absurd howthis passed peer review.
And then, of those 20 that theyactually screened on title and
(24:39):
abstract, you know they theylooked at 12 on full text and
they included nine and theydon't give reasons for the
exclusion on an individual level.
So it is just like I I justdon't even know.
I don't even know what to say.
You go from 13,000 to 70because quote, unquote,
irrelevant.
Yeah, you ever seen anything socrazy in your life?
Dr. Adam Sadowski (25:01):
No.
Dr. Joshua Goldenberg (25:01):
Oh my gosh, I'm putting that on the
wall.
I got to take that out and putit on the fridge, like it is,
like the strip.
That's got to be a teachingexample, as like what in the
world?
Dr. Adam Sadowski (25:10):
Yeah, no, that's a good.
That's in the world.
Yeah, no, that that's a good.
That's a good teaching exampleof like what not to do.
This whole paper, honestly,this whole paper is what not to
do it's so many red flags.
Dr. Joshua Goldenberg (25:20):
It's so many red flags.
So I mean it's just a greatexample of you know, if someone
just um, you know, was screeningthrough, I mean isn't bmc a
decent journal like this is justI don't think this is bmc
infectious agents and cancer.
I don't know that journal.
I just I don't think this isbmc infectious agents and cancer
.
I don't know that journal.
I mean I don't know the space,but yeah, this is just nuts.
It's like every red flag in theworld.
(25:41):
How in the world did it passpeer review?
And then I, it's just, yeah,that flow chart is just really
something else.
Okay, so basically we don'tbelieve a word we see.
And so what did they?
What did they find?
I feel like it's silly to evensay it.
So their overall meta analyticresult was an odds ratio of 2.57
(26:03):
.
So you're more than two and ahalf times likely to test
positive for this bovineleukemia virus.
I guess in your blood, I guessthe blood test, if you sorry, if
you have breast cancer, you'remore than two and a half times
more likely, or two and a halftimes the odds of testing
positive for this virus, whichwould suggest that you know it's
(26:24):
a.
It increases your risk by twoand a half times, or something
like that.
Now, of course, as it's veryclear, we don't believe a word
of this.
But even if we did, the otherissue is like I don't know what
the baseline, like it's, it'slike this is.
So you can't figure outabsolute effects with like these
(26:47):
types of studies, right?
So you say it's two and a halftimes, increases your risk two
and a half times.
Yeah, I don't, I don't know,like, how common are you getting
this disease, this virus?
And I don't know, I just don'ttrust any.
I, I just want to throw thewhole thing out.
I don't trust, I don't trust aword of it.
Now, that doesn't mean itdoesn't have this risk, right,
and it doesn't mean that, youknow, I.
Just so.
(27:09):
Here's the here's, the here's.
The question for relevance ishow many people walking around
on Earth have this virus in themat any given time?
And then of those, how manydevelop into breast cancer, like
that's the question, I suppose.
(27:29):
So this type of study would beenough to say there's a signal
there, but we can't figure outlike the absolute risk, like how
risky it is to be having milk,how risky it is to be having
pasteurized milk right?
So these are like goodquestions and it could be that
you know breast cancer ishorrible, so maybe we just want
(27:49):
to be super, super, super strict.
Dr. Adam Sadowski (27:51):
Well, also also, you know, remember it's an
association and it'sassociation and causation are
not the same thing.
This could have been peanutbutter jelly sandwiches for all
intents and purposes, likeseriously, right.
Dr. Joshua Goldenberg (28:05):
Well, let's talk about that for a
second.
You know, they don't, you know,and, to be fair, it's a
systematic review, so they'renot going into how the studies
did pick their controls.
But that's a big issue.
It's like I don't know.
There's probably a lot ofassociations between you know,
people that have breast cancerand other risk factors that are
associated with, I don't know,getting this stuff.
It may not necessarily be thevirus.
(28:27):
It's like you said, association, not necessarily causation.
That being said, that's how wefind harms and that's how we
find risk.
Right, that's why we do thesestudies.
But we just have to take themwith a grain of salt and at this
point, just like, yeah, thewhole salt shaker.
So I don't know.
I my take home is I have no idea.
Now I know a little bit moreabout what bovine leukemia virus
(28:48):
is.
I find it interesting.
I now know that your dad grewup on a farm and that you guys
still have the farm and that youhave milk in the fridge which I
think is so cool from the farm.
I think that's awesome and Iknow all these things, but I
don't know that there's anassociation with breast cancer.
It doesn't mean there's not,but it's just so terribly flawed
that I really just can'tbelieve a word.
Dr. Adam Sadowski (29:10):
Based on this paper.
We can't make anything reallyof it.
It was not, it was.
It was just a poor paper.
Dr. Joshua Goldenberg (29:16):
It might be the worst paper I've seen
this year.
It might be, yeah, it might bethe worst paper I've seen in the
past five years.
Wow so, and you know, it's justsuch an important take home
because the abstract looked fineLike.
I read the abstract first and Iwas like okay, so I'm getting a
sense of things, this isinteresting, I'm curious.
And then, as soon as you lookunder the hood, it just reeks
(29:37):
just absolutely reeks.
So this is why, yeah, go ahead.
Dr. Adam Sadowski (29:39):
Oh sorry, I was going to say that case
control studies are better formore rare events.
I don't know if we can qualifybreast cancer as rare yeah, but
how else would you find?
Dr. Joshua Goldenberg (29:51):
oh, you would do like cohorts.
Dr. Adam Sadowski (29:52):
You're thinking cohorts like um, like a
cohort study maybe a cohort,but like I don't know, it would
be better.
I don't know.
Dr. Joshua Goldenberg (29:59):
I just feel like it would be better if
it was more of a like, more of arare outcome yeah, I'm just
trying to think like how youwould even do that, because you
would need a cohort of peoplethat have this bovine uh virus
and then you'd have to watchthem, or you'd have a, you know,
you'd have great chart recordsof people and then you'd look at
(30:19):
the ones with breast cancer andthen you'd go back and see you
know how many of them had, youknow, leukemia exposure or
bovine leukemia virus exposure.
I don't know, I'm not sure thebest way to do this.
It's an interesting question,but I think, regardless, the
methods were just so horrific.
But that is going up on my wall, all right, ladies and
(30:40):
gentlemen.
Dr. Adam Sadowski (30:41):
In better news, in better news listeners.
I do have a paper that I aminterested in talking about
looking at.
It was published in the bmj andit was a meta-analysis.
Uh, looking at real bmj or bmjopen or bmj zillion things, bmj,
bmj bmj, bmj okay, all right,I'm listening, I'm listening and
(31:05):
it was a meta-analysis lookingat psilocybin for depression oh,
is that the one that everyonewas pissed off about?
I don't know.
I did share it with you.
I it was published recently.
Um, I do think that that peopleit seems it the psilocybin for,
uh, mental health stuff isreally kind of really expanding,
(31:27):
yeah, but with, like just thegeneral media and, yeah,
people's interest.
So I so I do think it's arelevant topic, uh, mental
health is also important and so,um, I think I think our
listeners would appreciate it.
I thought the paper was prettycool.
Um, so write into us if youguys want to, if you guys want
to hear it on the next episodeno, let's definitely do it.
Dr. Joshua Goldenberg (31:49):
I know which one you're talking about,
but the reason I held off on itbefore was I thought I saw on
the news that all thesestatisticians were writing in
saying they saw flaws in themethods and I was waiting for
like a formal author response,did they?
When you pulled the paper,which was probably more recently
, did they have a authorresponse at all?
(32:10):
Well, I bookmarked it, so giveme one second author response at
all.
Well, I bookmarked it, so giveme one second.
Sure, yeah, I was curious aboutthat.
Something about, I think whatit was, if I'm remembering
correctly, was they think therewas a.
They were assuming they putthings in a standard error
instead of standard deviation,and that is an easy mistake to
make on meta analysis extractionand it makes a huge impact on
(32:31):
the overall results because itimpacts the confidence intervals
.
And I think some statisticianswere looking at this.
They're like, wow, this is waytoo precise, there's something
missing.
And then they tried to look atthe data and they're like we
think they just made some errorshere.
Yeah, so let's wait to see whatthe formal author responses.
But yeah, then I definitely,because it could be that you
said, yeah, we made a mistake.
(32:53):
Mistakes happen, but it doesn'timpact the results of the study
.
In which case, yeah, Idefinitely want to review it.
Dr. Adam Sadowski (32:57):
Yeah, raised about standard error in
calculation of standardized meandifferences.
This is likely to haveoverestimated the benefits and
they're actively in reviewprocess of it.
Dr. Joshua Goldenberg (33:09):
Okay, so they're still doing it.
Okay, so let's hang tight untilthey actually review it,
because obviously, if there's noeffect after they fix the
errors, then so this is a thingtoo.
Is that when you start looking,when you have really sexy
topics like this, everyone looksreally really closely with like
fine-tooth comb, which isimportant but they can find all
sorts of tiny errors, like weput this in as a standard error
(33:30):
instead of a standard deviation.
That doesn't necessarily meanyou throw out the paper.
You know you have to say okay,like once we fix it, like what's
the actual result?
It could be a meaninglessdifference or it could make all
the difference.
So let's wait to see how thisone shuffles out.
Dr. Adam Sadowski (33:44):
Excellent, all righty.
Dr. Joshua Goldenberg (33:46):
Cool, all righty.
Thanks everybody.
Thanks for listening and we'lltalk to you next time.
If you enjoy this podcast,chances are that one of your
colleagues and friends probablywould as well.
Please do us a favor and letthem know about the podcast and,
if you have a little bit ofextra time, even just a few
seconds, if you could rate usand review us on Apple Podcasts
(34:07):
or any other distributor, itwould be greatly appreciated.
It would mean a lot to us andhelp get the word out to other
people that would really enjoyour content.
Thank you, hey y'all.
This is Josh.
You know we talked about somereally interesting stuff today.
I think one of the things we'regoing to do that's relevant.
There is a course we have on DrJournal Club called the EBM
Boot Camp.
That's really meant forclinicians to sort of help them
(34:28):
understand how to criticallyevaluate the literature, et
cetera, et cetera Some of thethings that we've been talking
about today.
Go ahead and check out the shownotes link.
We're going to link to itdirectly.
I think it might be of interest.
Don't forget to follow us onsocial and interact with us on
social media at DrJournalClubDrJournalClub on Twitter, we're
on Facebook, we're on LinkedIn,et cetera, et cetera, so please
(34:50):
reach out to us.
We always love to talk to ourfans and our listeners.
If you have any specificquestions you'd like to ask us
about research, evidence, beinga clinician, et cetera, don't
hesitate to ask.
And then, of course, if youhave any topics that you'd like
us to cover on the pod, pleaselet us know as well.
Introducer (35:08):
Thank you for listening to the Doctor Journal
Club podcast, the show that goesunder the hood of
evidence-based integrativemedicine.
We review recent researcharticles, interview
evidence-based medicine thoughtleaders and discuss the
challenges and opportunities ofintegrating evidence-based and
integrative medicine.
Be sure to visit www.
drjournalclub.
com to learn more.
Welcome to the Dr Journal Club podcast, the show
that goes under the hood ofevidence-based integrative
medicine.
We review recent researcharticles, interview
evidence-based medicine thoughtleaders and discuss the
challenges and opportunities ofintegrating evidence-based and
integrative medicine.
Continue your learning afterthe show at www.
(00:23):
d rjournalclub.
com.
Dr. Joshua Goldenberg (00:31):
Please bear in mind that this is for
educational and entertainmentpurposes o nly.
Talk to your doctor beforemaking any medical decisions,
changes, etc.
Everything we're talking aboutthat's to teach you guys stuff
and have fun.
We are not your doctors.
Also, we would love to answeryour specific questions on
drjournalclub.
com.
You can post questions andcomments for specific videos,
(00:55):
but go ahead and email usdirectly at josh at
drjournalclub.
com.
That's josh at drjournalclub.
com.
Send us your listener questionsand we will discuss it on our
pod.
Hello, this is Dr JoshuaGoldenberg and Dr Adam Sadowski
and we are here for take 17 oftoday's episode, where we are
(01:19):
desperately trying to beattechnology and the technology
gremlins which is a thing andactually record this stinking
podcast.
So, as I was saying before,Adam, this article that we're
talking about today was broughtto my attention by a patient of
mine who said hey, josh, wouldyou mind reviewing this meta
(01:39):
analysis?
And I just had this likeamazing moment, like I don't
think a patient has ever askedme to review a meta-analysis.
You just warmed my heart andthen I proceeded to completely
forget about it.
She like very kindly remindedme when I saw her the other day.
So, um, this is my attempt tomake amends and actually review
the article.
She had questions about uh,bovine, what is it bovine
(02:03):
something virus?
What is it bovine?
Bovine, what is it Bovinesomething virus?
What is it Bovine?
Dr. Adam Sadowski (02:06):
Bovine leukemia virus.
Dr. Joshua Goldenberg (02:08):
Leukemia virus.
Dr. Adam Sadowski (02:10):
And before we get into the episode, if
listeners, if you do send usstuff, do a one over and kind of
like, ask us what the questionis that you're looking for.
Don't just say is this a goodpaper, like is this good?
Because that's a relative termand we're not giving any medical
advice on this podcast either.
(02:31):
So if you have a paper, do likewho was it that sent in a paper
and had like six pinpointquestions to ask about it.
Dr. Joshua Goldenberg (02:41):
Was it Mark Mark Davis?
Dr. Adam Sadowski (02:43):
No, it wasn't .
It wasn't Mark Davis, it was,oh my gosh, dr Yarnell.
When Dr Yarnell did that, thatwas helpful because we knew sort
of like what we, what theintent of the paper was, outside
of our own interest.
So if you send us a paper, readit and give us your input and
give us a question.
If you don't know what you'rereading, go Dr.
(03:06):
Journal Club.
Dr. Joshua Goldenberg (03:08):
So let me give some background, because
in this case the patient gave melots of background information.
So, basically, I think she hadheard about this bovine leukemia
virus in the supply of milk andthat I think there were a
couple European countries Ithink she was saying that had
like gotten control of the virusin the bovine population
(03:28):
because there was this supposedconnection with breast cancer
and so she was concerned.
She wasn't sure if she wouldshould continue to drink milk or
not, or if it would be I thinkshe was traveling and if it
would be okay to have the milkin these countries.
So that was the question.
So very targeted question havethe milk in these countries?
So that was the question, sovery targeted question.
(03:48):
And then what I was excitedabout is you know, someone you
know, coming up with an actualmeta-analysis and knowing what
that was and be like, hey, whatdo you think?
So let's jump into it.
So let's see here, all right.
So, oh, of course, because thisis how this day is going, my
PDF player is off.
Dr. Adam Sadowski (04:05):
Well, that's okay, I've got it.
Dr. Joshua Goldenberg (04:07):
Oh, you got it.
Okay, great, why don't you setus?
You want to set us up with somebackground in methods and then
we can do like a critical evaland take home Keep it a little
short today, Sure sure, sure,sure.
Dr. Adam Sadowski (04:19):
So basically, what this study is looking at
is trying to look at some sortof association between this
virus known as bovine leukemiavirus, which I had never heard
of.
Dr. Joshua Goldenberg (04:29):
Me neither.
Dr. Adam Sadowski (04:30):
And the risk of breast cancer.
Dr. Joshua Goldenberg (04:32):
Oh, sorry , sorry, that reminds me, this
is what it was.
She had asked me about this andI said I have no idea.
So what does she do?
Because she's amazing, shecomes back with a freaking meta
analysis and asked me to thenopine, that's so awesome, right?
So anyway, yeah, go ahead.
So now I'm remembering.
Dr. Adam Sadowski (04:49):
Now it's all coming back, go ahead, yeah,
yeah, yeah.
And so this was a systematicreview and meta-analysis of case
control studies.
And so, for those who don'tknow what a case control study
is is you're taking cases andcontrols.
So there's the there.
Dr. Joshua Goldenberg (05:05):
So in this case, with breast cancer
and without breast cancer.
Dr. Adam Sadowski (05:09):
Yes, and so in a case control study, you
have cases and you have controls.
The controls are individualswho would not have some sort of
exposure or, excuse me, somesort of outcome of interest.
And these are, and you'recomparing them to cases, and
they're called cases becausethey already have the outcome of
(05:30):
interest that you're interestedin.
So in this case, the case wouldbe breast cancer and they're
taking people who have breastcancer already diagnosed and
comparing them to a group ofcontrols who, in theory, outside
of the breast cancer diagnosis,are very similar in their
(05:52):
demographic makeup, if you will,relative to the individuals
with breast cancer.
So you're trying your best tosay, hey, we have these two
groups of individuals.
You're trying your best to say,hey, we have these two groups
of individuals where the onlydifference is that one has
breast cancer and one doesn't.
(06:13):
Now, in reality, that's not.
That's not the case, becausethese are, these are, you know,
sort of low, low levelobservational studies.
So you know that there aregoing to be a lot of differences
, going to be a lot ofdifferences, and that's why we
like randomization is because ifyou're randomizing participants
to two different groups,there's basically a nice
evenness, if you will, betweenthe two groups.
If there's any sort ofdifferences, so those
(06:34):
differences get accounted for,whereas with this they don't.
Dr. Joshua Goldenberg (06:37):
Right and so, and there's some cases
where I mean can't randomize toget breast cancer.
Dr. Adam Sadowski (06:41):
So it's like like it's usually these harm
studies like this where you'relooking at these case control
studies because obviously youcan't randomize to that same
with like smoking sensation,stuff like that or you have a
very rare outcome where, yeah,you would have to recruit
millions of people just to getone outcome, or you would have
(07:02):
to get several thousand peopleand watch them, for you know 30
years before you get one outcome, or you would have to get
several thousand people andwatch them for you know, 30
years before you get one event.
And so it's just from apractical standpoint doesn't
make sense to do that.
So this is if you already havethe cases, you can kind of
compare them to the control, soit's kind of the next next best
option.
And then you look backwards intime and kind of look, for you
(07:25):
know, were they exposed tosomething or not?
And then, if they were, isthere an association between
that exposure and the outcome?
So in this instance we have ourcases which are individuals
with breast cancer, and then wehave our control people without
breast cancer and we're lookingback in time to see if people
(07:47):
who are exposed to the bovineleukemia virus had a greater
odds or greater likelihood ofdeveloping the outcome of
interest.
So in this case, breast cancer.
Dr. Joshua Goldenberg (08:00):
Well, so opposite in this case, right?
So it's like of those withbreast cancer.
Do they have an increased oddsof testing positive on this
virus test, right.
Dr. Adam Sadowski (08:09):
Okay, and so, to kind of set this all up,
they basically said that youknow, breast cancer is very
common.
I think our listeners are awareof that.
I don't think there's anythingyou know from that that we
really have to talk on, to talkon.
(08:29):
However, with regards to thebovine leukemia virus, basically
it belongs to a family of virusknown as retroviridae, so
they're retroviruses, and thenthere's different classes within
that and then the main hostwhere we would find them is in
cattle, but they can be in otheranimals as well.
And I thought it was funny thatthey said that the prevalence
of the virus infection is highin cattle and varies anywhere
(08:51):
from 39 to 100%.
Dr. Joshua Goldenberg (08:54):
That was mind-blowing yeah.
Dr. Adam Sadowski (08:56):
Yeah, so basically half or all cattle
have this virus.
Dr. Joshua Goldenberg (08:59):
Yeah.
Dr. Adam Sadowski (09:00):
And it can easily transmit through infected
blood and milk.
However, it causes disease inless than 5% of infected cattle.
So I mean, if you kind of thinkabout it, it's kind of like H
pylori in humans, where allhumans basically have H pylori.
The issue is when it causesdisease disease?
Dr. Joshua Goldenberg (09:27):
yeah, and then did you get a sense of
like is it only infectious tohumans if the cattle is actively
showing disease, or or if theyhave it right?
Um, I don't, that wasn't clearto me because it's like oh my
gosh, like I like a half to allof beef have it, or dairy have
it, and I don't know how that'sjust not being passed all the
time.
But but I guess if you'resaying only 5% are infected or
show disease, rather I supposethat's when you would be more
(09:49):
likely to spread the disease.
But it seemed like they weren'treally clear on how infection
to humans happened.
Dr. Adam Sadowski (09:55):
Well, they also said that the mechanism of
transmission to humans is notknown, with the exception that
raw milk consumption cantransmit the virus from cattle
to human population.
Dr. Joshua Goldenberg (10:06):
Right, so you got to watch the raw milk.
Did I ever tell you my raw milkstory Super fast?
So, okay, really really quick.
Dr. Adam Sadowski (10:13):
On the topic of tangents.
Dr. Joshua Goldenberg (10:15):
Yeah, no, I know, I know, Hold on.
You got to let me have this onebecause as I was reading it I
remembered it and I hadn'tremembered it since, like I
don't know, over a decade ago.
Anyway, long story short, in mywandering years I was
backpacking through CentralAmerica and I was living in
Guatemala for like a while and Iwas living with a Guatemala
Teca family and the mother wassort of like the surrogate
mother while I was there and itwas, like you know, didn't
(10:39):
really speak much English and itwas super fun.
Anyway, she was really into farout there natural things.
She was doing like these, likenaturally, essentially
naturopathic stuff, but out inlike the mountains of Guatemala,
and one morning she's like Josh, I have to take you, I have to
show you something.
So we hiked all the way up intothe mountains outside of town.
We were in a town called Sheilaand we go up and we just stop
(11:09):
at this like random farm, justwhips out a.
Um, we're on a hike and it'slike she's thirsty.
So she whips out her cup, walks, knocks on the on the farmer's
door, he comes out, he grabs thecup and he sits down in front
of the cow and just startsmilking it directly into the cup
and she's just down the hatchand off we go and we're on our
we're on the rest of our hike tosome like amazing, like sweat
(11:30):
lodge up in the mountains orsomething.
Anyway, that was.
That's my raw milk story.
Dr. Adam Sadowski (11:33):
My raw milk story is that, uh, the farm that
my dad grew up on, uh, is still.
They still own it and it's justone of his brother brothers
operates it and when I went togo visit we just, you know, we
put milk in a bucket and we justhad it from there and then,
like the next day, if you wantedmilk or something like you,
just open the fridge and so coolit was just literally farm
(11:56):
fresh milk, but yeah, notpasteurized or anything.
Dr. Joshua Goldenberg (11:59):
That is so cool.
Yeah, well, as far as we know,you don't have bovine leukemia
virus, although I guess we don'tknow for sure, it's always a
possibility.
Anyway, I love those stories.
Okay, so what we're talkingabout?
Oh yeah, tangents.
All right, so back we go totalk about the study and all
right.
So I think that's enough formechanism.
(12:19):
They were pretty.
The authors themselves werepretty light on details of how
this could work, except thatbasically saying, yeah, cancers
sometimes are associated withviruses.
We've got multiple examples ofthat.
There's evidence that breastcancer maybe 10, 20% of it may
be associated with differentviruses.
What about this one?
There's been multiple studies.
Let's meta-analyze it.
That was sort of like the setupas far as I could tell.
(12:40):
Anything else you want to addfor the setup?
Dr. Adam Sadowski (12:42):
No, that's it Okay, far as I could tell.
Anything else you want to addfor the setup?
No, that's it Okay.
Should we jump into methods andcritique thereof?
Yeah, so basically what theydid is they followed the PRISMA
reporting guidelines, which inall honesty, doesn't really mean
much.
And then what they did was allcase control studies that
investigated the virus infectionand breast cancers were
collected from several databases, and then that's kind of like
(13:08):
how they picked studies,eligibility criteria, looked at
case control and prevalencestudies in English between 1995
to January of 2020.
And then detection of the viruswas through random assays and
then they were excluded if theywere published in languages
(13:31):
other than English.
Studies other than breastcancer or other viruses that
were not bovine leukemia virusinfection in any sort of male
participants, and they also didnot include other systematic
reviews or meta-analyses, whichI thought was kind of an issue,
because there are ways where youcan kind of use that data.
Dr. Joshua Goldenberg (13:53):
They said .
They seemed to suggest no onehad done it before.
I don't know, maybe I misreadthat, but that's fine, Then then
.
Dr. Adam Sadowski (13:59):
okay, then I'll give them a pass.
Dr. Joshua Goldenberg (14:00):
But how would they know that?
If yes, how would they knowthat if?
Uh, I guess how would they knowthat if they hadn't done a
search?
So, to your point, just trustus, just just yeah.
Well, I think that just trustus is kind of throughout.
So there's no registration thatI can see.
Dr. Adam Sadowski (14:17):
Did you catch a registration?
No, I didn't see one yeah, sothey didn't register.
Dr. Joshua Goldenberg (14:20):
So if we think about like, okay, so, so
that's basically the method,just like you said, so if we
quickly go through the sevendeadly sins, so remember the
seven deadly sins for systematicreviews, so we've got.
Did they register Ideally apriori?
No, did they do.
Was their search quality decent?
Did they explain?
Dr. Adam Sadowski (14:37):
They didn't expand upon that.
Dr. Joshua Goldenberg (14:39):
Yeah, well, let's go through all these
.
Did they give rationale fortheir exclusion?
Did they do a risk of biasassessment?
Did they do adequatemeta-analytic methods?
Did they see how the risk ofbias impacted their
meta-analytic result?
And was there publication bias?
So these are the seven deadlysins.
These are the critical domainsof AMSTAR II.
If you have any one of these,be off.
(15:05):
Your entire systematic reviewis considered critically flawed
and you cannot rely on it at all.
Look, the thing is we don't dothis for money.
This is pro bono and, quitehonestly, the mothership kind of
ekes it out every month or so,right?
So we do this because we careabout this, we think it's
important, we think thatintegrating evidence-based
medicine and integrativemedicine is essential and there
(15:28):
just aren't other resources outthere.
The moment we find somethingthat does it better, we'll
probably drop it.
We're busy folks, but right nowthis is what's out there.
Unfortunately, that's it, andso we're going to keep on
fighting that good fight and ifyou believe in that, if you
believe in intellectual honestyin the profession and
integrative medicine and beingan integrative provider and
bringing that into theintegrative space, please help
(15:51):
us, and you can help us bybecoming a member on Dr Journal
Club.
If you're in need of continuingeducation credits, take our
NANSEAC approved courses.
We have ethics courses,pharmacy courses, general
courses.
Interact with us on socialmedia, listen to the podcast,
rate our podcast, tell yourfriends.
These are all ways that you cansort of help support the cause.
Help support the cause, solet's go through here.
(16:19):
So first, deadly sinregistration.
We both saw no evidence ofregistration, so we don't know
if they came up with theirmethods after the fact.
And that's of course, a problemwhen you're looking at outcomes
and you basically say, well,you're just reporting the stuff
that looks sexy, especially whenthere are some interesting
calls about their methodologies,which I think there there were
some.
So that's number one.
So already we've got one deadlyflaw search quality.
(16:41):
What do you think about thesearch quality?
They didn't really go into it.
Yeah, they didn't.
That's a problem.
Yeah, so there's no, thereshould be a in an abstract or
something, at the very least thepubmed search strategy.
There was not.
They gave a couple, a handfulof like mesh terms that they
basically riffed on, but that'sabout it.
(17:03):
Um, also, they said verystrange things.
I don't know if you caught this.
They said that theyindependently did the search,
which makes zero sense.
Dr. Adam Sadowski (17:10):
You don't independently do the search, you
independently screen the searchit may be a translation issue,
because this was, I think, basedin Iran.
Yes, yes, and so they may haveyou know.
It may just kind of be likeloosely translated incorrectly.
Dr. Joshua Goldenberg (17:27):
I think we give them that one.
I think you're probably rightabout that, because it would
just be so bizarre to do that.
That.
I think you're probably right.
Okay, so we'll give them a passon that.
But they don't really reporttheir search really at all.
I don't like that.
They only included studies inEnglish.
I don't think that makes anysense.
Why would you do that?
And I think you might beopening yourself up for bias.
So I would say concerns,critical concerns.
(17:51):
I don't know, probably, if youwanted to be strict about it,
but I didn't like the searchvery much.
Next, one exclusion rationaleDid you see anywhere a list of
studies they excluded on a studylevel that explained why for
each study?
Nope, nope, I didn't see it.
Either they did aggregate stuff, like we excluded eight for you
know they didn't have this orthey didn't have that, but there
(18:12):
is no individual study levelwhere you could go and say so.
We got another critical flawthere.
Did they do risk of biasassessment on the primary
studies?
Dr. Adam Sadowski (18:21):
Kind of.
Dr. Joshua Goldenberg (18:22):
They did, yeah, they did.
Was it Newcastle, Ottawa?
I think they used.
Dr. Adam Sadowski (18:26):
Well, so that's not necessarily.
Well, actually, yeah, that is arisk of bias tool, because they
had it as quality assessmentand so those two are different.
I view quality assessment assomething like a grade, whereas
this really should be a biasassessment which can then
influence the quality.
Dr. Joshua Goldenberg (18:47):
Yeah, and like you said earlier, language
matters.
I 100% agree with you.
I think, unfortunately, peopleare loosey-goosey with this
language and you see that a lotthey talk about study quality
when really what they mean isrisk of bias, to your point.
Maybe it's a translation thingtoo.
But yeah, so they did do a riskof bias assessment.
They only included studies thatscored high, like that did well
(19:12):
on the risk of bias assessment,which I thought was interesting
.
It was like sort of a strictinterpretation.
They had a threshold cutoff andthey said we only are basically
looking at the studies abovethis.
It threw me a bit, becausecalls like that it's like why
and when did you decide to dothat, and I would be much more
comfortable.
Dr. Adam Sadowski (19:32):
And why that score?
It seems arbitrary.
Dr. Joshua Goldenberg (19:35):
And why that score?
Yeah, is that standard?
Is that considered a standardhigh level?
And again, like if we had a apriori registration, we'd say,
oh yeah, this is what they planto do.
They were worried about risk ofbias studies, but we just have
to, kind of like you said, taketheir word for it now.
So I give them a pass on therisk of bias assessment, but I'm
a little questioning abouttheir inclusion.
Dr. Adam Sadowski (19:57):
What I would have done, too, was I would have
included all of them and then,if you wanted to do like a
sensitivity analysis, say, okay,we're only going to include
studies with a score of, let'ssay, four or higher.
Yes, and we're saying four orhigher because and then have
(20:17):
evidence saying why, why thatnumber, as opposed to just an
arbitrary number, saying, oh,this, this sounds like it's a
higher quality.
Dr. Joshua Goldenberg (20:24):
Yeah, that's the right way to do it,
in my opinion.
You, you have all the evidenceand then, exactly, you view risk
of bias as a sensitivityapproach.
So I agree with you on that one.
I have seen other people dothis.
I agree with you though.
But yeah, and then I think theymeta-analyzed appropriately.
I didn't see any technicalproblems there.
The risk of bias impact ontheir overall estimate is kind
(20:47):
of moot, because they onlylooked at low risk of bias
studies and then publicationbias.
They did visual inspection andstatistical analyses, which is
appropriate, but the rule ofthumb for publication bias is
you don't do those if you've gotunder 10 studies, and they only
meta-analyze nine.
So it's underpowered.
(21:09):
So for them to say we didn'tsee any evidence of publication
bias, I mean it doesn't reallymean anything.
It's an underpowered test atthat point.
Dr. Adam Sadowski (21:27):
No one's going to see evidence of
publication bias.
So I don't know, I don't know amethodologist on their team,
yeah, and just kind of used sortof like very rudimentary
methods to this.
Dr. Joshua Goldenberg (21:39):
Yeah, I agree.
So I think my take home isthey've got three, three and a
half critical flaws.
This is a critically flawedsystematic review.
We'll talk about the results ina second, but pretty much I
don't trust the results beforewe even kind of talk about them.
Is my take home on that one?
Anything else on methods youwant to add?
Dr. Adam Sadowski (21:59):
No, that's it .
Dr. Joshua Goldenberg (22:00):
OK, cool, and I think you had the same
impression, sort of talking inthe green room there as well.
Ok, so let's talk about results.
So both of us are skepticalabout what the results will be,
but we'll.
Oh, they also had like crazyheterogeneity 80, not crazy, but
very high, 85 percent 85percent yeah, yeah, super
(22:24):
heterogeneous.
Um, they tried to exploreheterogeneity but I don't see
that they talk about.
Did I miss the results of theof the subgroup analyses?
Dr. Adam Sadowski (22:36):
nope, but.
But I think what we should sayis that they apparently they
started off with 13 000 studiesoh yeah oh right, so they start
off with 13 000 studies, andthen, of 70 that that remained,
uh 61 were included, and sothat's how they got to nine.
Honestly, I'm very skepticalthat their search strategy had
(22:58):
any sort of relevancy.
It's probably 13,631.
Dr. Joshua Goldenberg (23:03):
It makes no sense.
Dr. Adam Sadowski (23:03):
Probably picked up anything that had
bovine leukemia virus in thetitle, so it could have been
like you know BLV and rats.
It probably was not a goodsearch study.
Dr. Joshua Goldenberg (23:11):
You know BLV and rats it probably was not
a good search study.
So your point is the uppernumbers really high, so it
wasn't a very specific search.
Like I agree, you're probablyright and with everything else
we see, I don't know that wegive them a pass to say, oh,
they were trying to be overlysensitive.
But look at the next thing inthe Prisma flow chart.
So it goes from 13,608 to afterremoving duplicates and quote
(23:35):
irrelevant material or whatever70.
70.
What?
What does that mean?
So you remove duplicates?
Maybe I don't know.
You remove 1,000, 2,000.
So there's still probably, likeI don't know, 10,000 studies
and then they remove irrelevant.
Who's removing irrelevant?
Based on what right that soundslike?
(23:56):
I don't know.
Is that?
Do they mean title and abstract?
But no, they don't, becausethen they take of those 70, 20,
they only are screening 20 ontitle and abstract.
Like just to give peoplecontext, like we will often
screen thousands on title andabstract and somehow they get to
20 by quote removing irrelevantstudies in some mysterious way.
(24:17):
I don't know what that means.
Removing irrelevant studies?
It is the biggest red flag I'veever seen on a Prisma flowchart
.
I don't know how this passedpeer review.
Maybe this is not a legitjournal, I don't even know,
maybe it's one of thesepredatory journals.
This is just beyond absurd howthis passed peer review.
And then, of those 20 that theyactually screened on title and
(24:39):
abstract, you know they theylooked at 12 on full text and
they included nine and theydon't give reasons for the
exclusion on an individual level.
So it is just like I I justdon't even know.
I don't even know what to say.
You go from 13,000 to 70because quote, unquote,
irrelevant.
Yeah, you ever seen anything socrazy in your life?
Dr. Adam Sadowski (25:01):
No.
Dr. Joshua Goldenberg (25:01):
Oh my gosh, I'm putting that on the
wall.
I got to take that out and putit on the fridge, like it is,
like the strip.
That's got to be a teachingexample, as like what in the
world?
Dr. Adam Sadowski (25:10):
Yeah, no, that's a good.
That's in the world.
Yeah, no, that that's a good.
That's a good teaching exampleof like what not to do.
This whole paper, honestly,this whole paper is what not to
do it's so many red flags.
Dr. Joshua Goldenberg (25:20):
It's so many red flags.
So I mean it's just a greatexample of you know, if someone
just um, you know, was screeningthrough, I mean isn't bmc a
decent journal like this is justI don't think this is bmc
infectious agents and cancer.
I don't know that journal.
I just I don't think this isbmc infectious agents and cancer
.
I don't know that journal.
I mean I don't know the space,but yeah, this is just nuts.
It's like every red flag in theworld.
(25:41):
How in the world did it passpeer review?
And then I, it's just, yeah,that flow chart is just really
something else.
Okay, so basically we don'tbelieve a word we see.
And so what did they?
What did they find?
I feel like it's silly to evensay it.
So their overall meta analyticresult was an odds ratio of 2.57
(26:03):
.
So you're more than two and ahalf times likely to test
positive for this bovineleukemia virus.
I guess in your blood, I guessthe blood test, if you sorry, if
you have breast cancer, you'remore than two and a half times
more likely, or two and a halftimes the odds of testing
positive for this virus, whichwould suggest that you know it's
(26:24):
a.
It increases your risk by twoand a half times, or something
like that.
Now, of course, as it's veryclear, we don't believe a word
of this.
But even if we did, the otherissue is like I don't know what
the baseline, like it's, it'slike this is.
So you can't figure outabsolute effects with like these
(26:47):
types of studies, right?
So you say it's two and a halftimes, increases your risk two
and a half times.
Yeah, I don't, I don't know,like, how common are you getting
this disease, this virus?
And I don't know, I just don'ttrust any.
I, I just want to throw thewhole thing out.
I don't trust, I don't trust aword of it.
Now, that doesn't mean itdoesn't have this risk, right,
and it doesn't mean that, youknow, I.
Just so.
(27:09):
Here's the here's, the here's.
The question for relevance ishow many people walking around
on Earth have this virus in themat any given time?
And then of those, how manydevelop into breast cancer, like
that's the question, I suppose.
(27:29):
So this type of study would beenough to say there's a signal
there, but we can't figure outlike the absolute risk, like how
risky it is to be having milk,how risky it is to be having
pasteurized milk right?
So these are like goodquestions and it could be that
you know breast cancer ishorrible, so maybe we just want
(27:49):
to be super, super, super strict.
Dr. Adam Sadowski (27:51):
Well, also also, you know, remember it's an
association and it'sassociation and causation are
not the same thing.
This could have been peanutbutter jelly sandwiches for all
intents and purposes, likeseriously, right.
Dr. Joshua Goldenberg (28:05):
Well, let's talk about that for a
second.
You know, they don't, you know,and, to be fair, it's a
systematic review, so they'renot going into how the studies
did pick their controls.
But that's a big issue.
It's like I don't know.
There's probably a lot ofassociations between you know,
people that have breast cancerand other risk factors that are
associated with, I don't know,getting this stuff.
It may not necessarily be thevirus.
(28:27):
It's like you said, association, not necessarily causation.
That being said, that's how wefind harms and that's how we
find risk.
Right, that's why we do thesestudies.
But we just have to take themwith a grain of salt and at this
point, just like, yeah, thewhole salt shaker.
So I don't know.
I my take home is I have no idea.
Now I know a little bit moreabout what bovine leukemia virus
(28:48):
is.
I find it interesting.
I now know that your dad grewup on a farm and that you guys
still have the farm and that youhave milk in the fridge which I
think is so cool from the farm.
I think that's awesome and Iknow all these things, but I
don't know that there's anassociation with breast cancer.
It doesn't mean there's not,but it's just so terribly flawed
that I really just can'tbelieve a word.
Dr. Adam Sadowski (29:10):
Based on this paper.
We can't make anything reallyof it.
It was not, it was.
It was just a poor paper.
Dr. Joshua Goldenberg (29:16):
It might be the worst paper I've seen
this year.
It might be, yeah, it might bethe worst paper I've seen in the
past five years.
Wow so, and you know, it's justsuch an important take home
because the abstract looked fineLike.
I read the abstract first and Iwas like okay, so I'm getting a
sense of things, this isinteresting, I'm curious.
And then, as soon as you lookunder the hood, it just reeks
(29:37):
just absolutely reeks.
So this is why, yeah, go ahead.
Dr. Adam Sadowski (29:39):
Oh sorry, I was going to say that case
control studies are better formore rare events.
I don't know if we can qualifybreast cancer as rare yeah, but
how else would you find?
Dr. Joshua Goldenberg (29:51):
oh, you would do like cohorts.
Dr. Adam Sadowski (29:52):
You're thinking cohorts like um, like a
cohort study maybe a cohort,but like I don't know, it would
be better.
I don't know.
Dr. Joshua Goldenberg (29:59):
I just feel like it would be better if
it was more of a like, more of arare outcome yeah, I'm just
trying to think like how youwould even do that, because you
would need a cohort of peoplethat have this bovine uh virus
and then you'd have to watchthem, or you'd have a, you know,
you'd have great chart recordsof people and then you'd look at
(30:19):
the ones with breast cancer andthen you'd go back and see you
know how many of them had, youknow, leukemia exposure or
bovine leukemia virus exposure.
I don't know, I'm not sure thebest way to do this.
It's an interesting question,but I think, regardless, the
methods were just so horrific.
But that is going up on my wall, all right, ladies and
(30:40):
gentlemen.
Dr. Adam Sadowski (30:41):
In better news, in better news listeners.
I do have a paper that I aminterested in talking about
looking at.
It was published in the bmj andit was a meta-analysis.
Uh, looking at real bmj or bmjopen or bmj zillion things, bmj,
bmj bmj, bmj okay, all right,I'm listening, I'm listening and
(31:05):
it was a meta-analysis lookingat psilocybin for depression oh,
is that the one that everyonewas pissed off about?
I don't know.
I did share it with you.
I it was published recently.
Um, I do think that that peopleit seems it the psilocybin for,
uh, mental health stuff isreally kind of really expanding,
(31:27):
yeah, but with, like just thegeneral media and, yeah,
people's interest.
So I so I do think it's arelevant topic, uh, mental
health is also important and so,um, I think I think our
listeners would appreciate it.
I thought the paper was prettycool.
Um, so write into us if youguys want to, if you guys want
to hear it on the next episodeno, let's definitely do it.
Dr. Joshua Goldenberg (31:49):
I know which one you're talking about,
but the reason I held off on itbefore was I thought I saw on
the news that all thesestatisticians were writing in
saying they saw flaws in themethods and I was waiting for
like a formal author response,did they?
When you pulled the paper,which was probably more recently
, did they have a authorresponse at all?
(32:10):
Well, I bookmarked it, so giveme one second author response at
all.
Well, I bookmarked it, so giveme one second.
Sure, yeah, I was curious aboutthat.
Something about, I think whatit was, if I'm remembering
correctly, was they think therewas a.
They were assuming they putthings in a standard error
instead of standard deviation,and that is an easy mistake to
make on meta analysis extractionand it makes a huge impact on
(32:31):
the overall results because itimpacts the confidence intervals
.
And I think some statisticianswere looking at this.
They're like, wow, this is waytoo precise, there's something
missing.
And then they tried to look atthe data and they're like we
think they just made some errorshere.
Yeah, so let's wait to see whatthe formal author responses.
But yeah, then I definitely,because it could be that you
said, yeah, we made a mistake.
(32:53):
Mistakes happen, but it doesn'timpact the results of the study
.
In which case, yeah, Idefinitely want to review it.
Dr. Adam Sadowski (32:57):
Yeah, raised about standard error in
calculation of standardized meandifferences.
This is likely to haveoverestimated the benefits and
they're actively in reviewprocess of it.
Dr. Joshua Goldenberg (33:09):
Okay, so they're still doing it.
Okay, so let's hang tight untilthey actually review it,
because obviously, if there's noeffect after they fix the
errors, then so this is a thingtoo.
Is that when you start looking,when you have really sexy
topics like this, everyone looksreally really closely with like
fine-tooth comb, which isimportant but they can find all
sorts of tiny errors, like weput this in as a standard error
(33:30):
instead of a standard deviation.
That doesn't necessarily meanyou throw out the paper.
You know you have to say okay,like once we fix it, like what's
the actual result?
It could be a meaninglessdifference or it could make all
the difference.
So let's wait to see how thisone shuffles out.
Dr. Adam Sadowski (33:44):
Excellent, all righty.
Dr. Joshua Goldenberg (33:46):
Cool, all righty.
Thanks everybody.
Thanks for listening and we'lltalk to you next time.
If you enjoy this podcast,chances are that one of your
colleagues and friends probablywould as well.
Please do us a favor and letthem know about the podcast and,
if you have a little bit ofextra time, even just a few
seconds, if you could rate usand review us on Apple Podcasts
(34:07):
or any other distributor, itwould be greatly appreciated.
It would mean a lot to us andhelp get the word out to other
people that would really enjoyour content.
Thank you, hey y'all.
This is Josh.
You know we talked about somereally interesting stuff today.
I think one of the things we'regoing to do that's relevant.
There is a course we have on DrJournal Club called the EBM
Boot Camp.
That's really meant forclinicians to sort of help them
(34:28):
understand how to criticallyevaluate the literature, et
cetera, et cetera Some of thethings that we've been talking
about today.
Go ahead and check out the shownotes link.
We're going to link to itdirectly.
I think it might be of interest.
Don't forget to follow us onsocial and interact with us on
social media at DrJournalClubDrJournalClub on Twitter, we're
on Facebook, we're on LinkedIn,et cetera, et cetera, so please
(34:50):
reach out to us.
We always love to talk to ourfans and our listeners.
If you have any specificquestions you'd like to ask us
about research, evidence, beinga clinician, et cetera, don't
hesitate to ask.
And then, of course, if youhave any topics that you'd like
us to cover on the pod, pleaselet us know as well.
Introducer (35:08):
Thank you for listening to the Doctor Journal
Club podcast, the show that goesunder the hood of
evidence-based integrativemedicine.
We review recent researcharticles, interview
evidence-based medicine thoughtleaders and discuss the
challenges and opportunities ofintegrating evidence-based and
integrative medicine.
Be sure to visit www.
drjournalclub.
com to learn more.
Popular Podcasts
Fudd Around And Find Out
UConn basketball star Azzi Fudd brings her championship swag to iHeart Women’s Sports with Fudd Around and Find Out, a weekly podcast that takes fans along for the ride as Azzi spends her final year of college trying to reclaim the National Championship and prepare to be a first round WNBA draft pick. Ever wonder what it’s like to be a world-class athlete in the public spotlight while still managing schoolwork, friendships and family time? It’s time to Fudd Around and Find Out!
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.
24/7 News: The Latest
The latest news in 4 minutes updated every hour, every day.