it's a rude awakening and mornig welcome to do with the uh... third week of
medical school for you you might have noticed that our
cohort of medical students has that doubled
in size if you guys have noticed you if you're here first of all the job finding
this other lecture hall sorry work
jumping you from place to place but this is part of
trying to revamp
all of our lecture halls and so we had to do this in a stage process those of
you that understands gantt charts
and construction
will uh... will sympathize but you found the place
in north lecture hall now are your colleagues here and suits
they are a great source of advice
and uh... and uh... being able to and sort of queries about different staff so
now you've got your built-in
counselors uh... here but they're also going to be very busy as you notice they
probably probably noticed they started about an hour before you did so
for
that's what you have to look forward to it here
that that
uh...
hope you guys survived your first quiz hopefully it wasn't too painful i know
many people ask will they be medical decision making
stuff on the quiz and the answer to that was
uh...
remember that genetics in pathology or the big components of the quizzes and
that we in india and we have assignments so you turned in your first assignment
last thursday at small groups
uh... i'm in the process of reviewing them
they will get back to you in your mail boxes
uh... so you will be have them to study from
i will also when i return them to you you should pay attention on c_ tools all
publisher ultimate which will also have the answer key
to interview uh... assignments
so there's no hidden doctors here it'll be a turkey will give you an explanation
to each of the questions that way you can look at your answer what banter in
turkey was any notes that you had
and reconcile and if there are any
other questions certainly we're here to help you
you have another small group tomorrow afternoon
that will largely be based on material that we cover today
uh... hopefully if you guys have had a chance to get a jump start on that i try
to post in a week in advance
you're more then welcome to
uh... reading ahead is hopefully fine encouraged if you want to do want to
that's totally fine as well
there should be enough time to be able to complete that again it's the same
protocol
bring it to your small group still discuss that with here
co students in your small group silkair and then returned them
uh... tournament and then i'll be returning to you in a timely fashion
any questions about the logistics of this course for this part of this force
so why don't we go ahead and get started
uh...
today we're going to be for we're gonna be picking up a little bit where we left
off
last time
and he wants start by declaring uh... any industry relationships
that i might add to contacts that meet your otherwise
in the answer is
certain factor
uh... dancers is i have not been
to disclose
so nothing that would uh... interfere with my ability to present you an
objective view of uh... medical decision made
so our first just returning to where we left off with their first thread
this is around information retrieval focusing on asking in acquiring
if you remember and
after last monday we left off by talking about the way the structure well
foreground question and these are sort of that
uh... fundamental tools that were required to
af but good questions get the information from the literature and then
interpret and apply them as a way to focus a little bit just to revisit
this tool that we talked about
this was the pico tool that encourage you to just use it as a tool basically
it's a way of specifying the different elements in your question there will be
important
tour it ought to be able to sort out the appropriate answers
and we think it's important to be able to do with in advance
because by doing it in advance
uh... you're really able to focus on what you need and what your patients
need
so in order to practice doing this went to ask you to do is to look at this case
and practice with your partner
jotting down the foreground
uh... question so let me go over the case real briefly
because we're gonna be using this uh... moving forward
so this is now this is a forty two-year-old woman
who comes to her primary-care practitioners office
for follow-up of her diabetes and you're the medical student
she's currently on libby ride
ten milligrams twice daily
however her blood sugars still stay elevated despite being on that
medication delivery right
after you see this patient
you're attending asked whether you think
she should admit foreman to her regimen
pretend like you know what would your ideas and pretend like you know what
metformin is you may not but these are both
uh... it is that we use in diabetes
we'll be right is the sole final you react
and metformin is uh... another agent that we use
uh... packets dvd
uh... and i cant really pronounce what that actually stands for it's a very
difficult word to pronounce but
suffice it to say good beer i can see his your um... insulin
uh... usa secretion but metformin improves your sensitivity uh... to
insulin is well or that your body makes
so let's say you know all of that
and the question i would ask you to do is to start putting on
your hat as if you were a clinician just to get a sense of what
these kind of foreground questions are about remember therefore important
components
for a foreground question you have to define the patient population that
you're interested in
you have to define the intervention
that you're interested in
the comparison group that would be part of the study that might help you answer
the question andy outcomes of interest
that you would be that you in your patient would be interested in
this will help you then scanned the literature to figure out what are the
articles that would be most relevant
for this particular case
so i'd like you did it was turned your partner and come up with one
that would meet all four categories it's a fairly straightforward exercise but
wanna make sure that you get
such answer practice that's so spent a couple minutes doing that and we'll talk
about it
a
okay three parking lot with remember that really
nobody answers here because
every single uh... every single answer that you would give each of the four
different categories would have some debate around
whether the article that you retrieved with those particular characteristics of
the study population
would actually help you answer your question
or not and the degree to which it would do that so let's just hear some of the
questions what i'd like you to do is not the same like he was ex and i was
uh... was why
i'd like to see if you could stated in the form of a question one that would
contain all four
of those different components
just a little hint
i might ask something like this uh... on one of the either the assignments
or certainly
while our final examination as well so who wants to take a stab at it
them
uh...
okay great so here let me let me restate this
in women with diabetes
what is the effect of metformin plus glider ride
blood sugar levels compared to drive me right along
so let's see if we got all the before components in their is that patient was
women with diabetes your intervention was metformin it would be right together
versus delivery right alone in the outcome you're interested in
was improvement in her blood sugar levels okay
so let's break that down the patient population is that were women with
diabetes was that it did anyone have something different
then women with diabetes here
awesome al you specified in age cutoff so women with diabetes over forty ok any
other
variabilities there
asel na specifying gender so just all patients with diabetes let's back up and
think about that
limelight it so that the question would be if we're to get an article
that had
all ahead men and women
in the past study population
would we say that's ok to extrapolate the results
and then apply to this patient population
and so you said
potentially that would be ok any reason to think that verb rationale
what goes through your mind as you're making that call
but the answer being that date one of the rationale might be fifty-year
defined studies where you have
both genders represented as opposed to
one gender alone so that's one certainly one consideration what might be another
consideration you would use
uh... so now you're talking you're getting even more specific saying
impatience
who are
poorly controlled on good be ride with diabetes
what about the comparison group purses uh... verses the intervention so that we
another
shape that you would be there
but that you might use backing up to the gender issue
the question i would ask you to ask and we ask this question all the time does
the disease manifest differently or act differently
in one gender verses another
does the disease manifest if really inpatient over forty
rice's those that might be younger than forty
those would be the questions that you would be asking yourself and remember
you have to build some background knowledge about this subject before
being able to ask the most sophisticated
foreground question
i'm trying to know a little bit about the pathophysiology
but it's reasonable to have those different want uh... those those
different shades of variation
in the patient
the intervention was metformin plus we'll be right did anyone have a
different intervention
oddly be what we're thinking about the kind that we're not talking about
stopping the glitter ride and adding metformin
but in some cases you might be looking for head to head comparison
and in fact if you're thinking about it from a drug company standpoint they may
be interested in head to head comparisons because they're trying to
prove one
at the at the efficacy of one drug over another
if you're thinking about it from the standpoint of
of uh... pathophysiology you might be interested in head to head comparisons
but if you're thinking about it in the practical sense we often might be
looking at
adding and agent to an existing regimen
those are less commonly found
in the literature on just a tad
and so you may be stuck saying well i don't have an additional
uh... i don't have a study that shows the addition of metformin
and so you would have to extrapolate
from head to head comparison
which is tricky did you
certainly beyond the scope of this course but keep in mind those of the
questions that we entertain as positions as for reading the literature
now one of the outcomes that was was mentioned was improvement in blood sugar
so first of all how would we measure that
but voz votes
okay so you could be looking at that's the blood sugar which have been one
marker of diabetes hemoglobin a one c which alert next year
is a eleven for a test that we get that it looks at patients long-term control
our blood sugar at least medium control over the past three months
so that be a good outcome
to specify so you could get that level of specificity and you might find
studies that look at just after larger verses does that look at a one c and you
would have to decide which ones
for me in my patient now would be important consideration
any other types of outcomes you guys looked at
or anyone specified besides blood sugar improvement
basil side effects might be another outcome that you would look at what sort
of side effects might be worth we'd be worried about a few
if you know any
so one that i might be worried about is would i be dropping this patient's blood
sugar too low
to the point that they have hypoglycemic events
so that would be something to be thinking about
but absolutely remember this is a therapeutic question that your asking
and as if they're peter question there are unintended or sometimes
uh... known side effects of the different genes that we
that we use and so looking at the adverse events
would be another important outcome
so keep in mind this is just an exercise but to wall
to get us to where we dot where we need to go so that when we look at the
literature
we know what we're looking at
that is the point of the foreground question
now this is up there
foreground question before i questions about their feet
later on in this lecture really talking about or run questions
as it pertains to diagnostic tests
again to get distinct types of questions
but both equally important here a couple of examples that we that were uh... that
would be reasonable i think you guys came in kimba up with these in tight to
die but if that was one thing we didn't talk about the fact that this woman
is a tight to diabetic
she may be insulin requiring more insulin
resist uh... you know that we talk about that one person so i can fight one being
autoimmune
more likely to happen upon early onset
tight too
uh... not necessarily requiring insulin
uh... and so you might want to distinguish that studies that you're
looking at
but then there's a question is metformin good write better than the bread alone
in lower bucks ordered that was something that you guys came up with and
here's the side-effect question among women with type two diabetes
are there more instances of low blood sugar of insufficient on both metformin
it would be right
when compared with we'll be right along
so that you guys came up with this fairly straightforward exercised but
keep in mind level of specificity is important because you're gonna be faced
with a ton of different studies
you're gonna have to work through to figure out which are the ones that are
most relevant tumi and the patient that you're working with what are the
important outcomes to that may be very different
and the outcomes that you are interested in and so it's important vehicle to
specify that of prop yes
went
at
so it literature doesn't exist uh... what do you do that is probably
uh... the hardest question we face as clinicians
there is a when i'm gonna ask you to i'm not gonna be able to answer that
completely
but as we build our course over the next three years what you're going to get a
sense of
is that there is a hierarchy of evidence
meaning that as
certain studies take on certain study characteristics both in terms of how
they're designed and how well their implemented the level of evidence that
they provide become stronger or weaker
and so it's not necessarily do i have
is there no studies out there
what are their studies out there that are less well done and so what do i do
with those
compared to studies that are really well done
keeping in mind that the studies that are really well done are actually less
frequently encounter
and those studies that are not so well done or studies that are
observation as opposed to control clinical trials
so the answer your question is i don't have the answer now but that is exactly
going to be the point of the next three years
what do you do when you're faced with a quandary we're gonna try to party
conceptual model that will on full
that you'll get more comfortable
there many sources the foreground questions these are the pics precise
questions if you go to medline four
or that you will go to a practice guidelines or you'll use evidence-based
databases and all of these sorts of
of uh... of resources will be introduced to you
as we go through
so building on those questions then
we do need to then figure out what is the data that we're getting and how do
we interpret
and so as i mentioned therapy types of questions are
are very important part
of what we do is the nation's they seem to be
the most natural thing you would assume positions do which is prescribed
treatment
and figure out whether it's
making a difference or not
however it is not the most fundamental thing that we do in fact
therapeutic questions are very sophisticated questions
that we actually don't cover much about their pete this year
we do it in your second year as you start tackling pathophysiology
this year
the question we want you to start thinking about
what is going on
is that you all a g of why what i'm so the the clinical manifestations
of the disease
and so that really focuses on diagnostic reasoning and diagnostic test and so
we're gonna spend the rest of our time today focusing on diagnostic tests
so here are the learning objectives for the rest of today by the end by the end
of this lecture and honestly by the end of your small groups tomorrow because
you're gonna have to work through these concepts in small groups it's gonna be
mainly a superficial
covering today of the concept
and the diving into it with your simon in small groups are really where the
learnings going to happen
but by the end of this series of sessions
you should be able to do some
fairly basic diagnostic
diagnostic question formulation
you should be able to define and uh... calculate
sensitivity specificities and the predicted values for different
diagnostic test for an introduce that concept you today and tomorrow
and you should be able to explain how risk factor
that god can thrive prior probabilities
and how this concept relates to prevalence
and then finally you should be able to modify probabilities from test results
through on number of different mechanisms
we introduce you to the concept obeys probabilistic reasoning as a way of
modifying probabilities over time
today we're gonna use
to buy two tables which is a of more straightforward
easy to conceptualize and visualize way of modifying probabilities
but you'll get more and more practice with using that keep in mind that it is
just as good as base so these are presented to you as you should be one
over the other represented the us items to put in your toolbox in portland
out
at different points when the need arises
there also other tools that are available that will introduce to you one
called likelihood ratios
and you'll get a chance to practice these
in your assignments and in your smokers
so just like we had the odyssey as a case for introducing you to use
probabilistic reasoning this time really immerse yourself in a clinical case and
i want you to think about this again just with uh...
limited amount of knowledge you have about this condition of this disease
whatever you have this fall
but bring to bear your experience as we work through this case during the
remaining a bit the remainder of this like
so the cases is sixty year old man
who does not have heart disease
who presents with sudden onset of shortness of breath
dismissed is a term that we use
so here is a politically description of the problem that you can see
yesterday after he flew in from california the day before
he'll blokes suddenly in the middle of the night at three in the morning with
sudden shortness of breath
so we woke up gasping for air at three in the morning
and he tells you
that you ask them one question which is
well was it bad when you were lying down and that's why you setup or was it worth
when you or is it about the same regardless of whether you're setting up
ur lying down
because the people maybe was worse than usual you said you know what
actually is it
any different online down if i'm sitting up
i'm still
feeling short of breath and it won't be up in the middle of the night
all right so that is your initial chief complaint
this is something that you'll get used to uh... as you do your data uh...
queries from uh... from patients at your data gathering
from from different
but you being a good clinician
you start asking some follow-up questions just like a good clinician
uh... or good mccain sort of building on the mechanic model that we introduce you
to a week ago
so you ask him what other symptoms were you feeling at the time
now as you get more sophisticated you will be asking more specific questions
right now
sort of the about what i would expect
and what seems to be able to do what else we feeling at the time
well he says does not testing
he doesn't have a leg pain he doesn't notice any swelling of his leg
he says idea just come back from a long plane ride he flew in from california
solicit was about five hours
nonstop
and he's had no problems like this before that he knows
this shortness of breath
he takes one aspirin every day and he does a smoke a pack of cigarettes
everyday
so that's kind of the next phase of diagnostic
intake
so the question that faces all of us just like the mechanic faces
is to be able to build a differential diagnosis you remember me mentioning
well we as clinicians
still differential diagnoses all the time
and basically differential diagnosis is a list
of possibilities with associated likely that's with associated probabilities
so as we mentioned last time if you can p of a particular condition you'd be
saying that the likelihood that
this particular condition is the reason for the shortness of breath
is x percent that's how you would write that down
and what you would do is you place it in descending order of likelihood and you
would be talking about wine
if you could get this
conceptual approach
jupe all your differential diagnoses
you will do well in medicine because this is how we talk
now we don't do it necessarily in such mathematical discrete models
is exactly what we talk when we talk with another position we like you know
what
i think this patient has colon cancer it's definitely more likely that he's
got colon cancer than he has hemorrhoids
that's kind of how we speak in barely in formal settings
when we're discussing
uh... the case uh... a particular patients case in trying to understand it
yala g
what we're really doing though is that words generating a differential
diagnosis and it is the regardless of what field you're going to do
you'll be doing this over and over again
so you get to your first one today
so now what i'd like you to do
is think about
what possibilities may be going on with this particular time
talk it over with your partner list two or three things that might be going on
and i will talk about what i think might be going on
e
okay productive well on the five because it's probably arctic every different
about yourself
at this stage that you're at
but it's not wrong to try
so let's just hear something you don't have to give me a probability or
anything like that
just give me some possibilities of what might be going on
all materialism versus congestive heart failure okay so we've got pulmonary
embolism
congestive heart failure what else do we go
sleep apnea okay great other things yeah
guilty gear emphysema while you guys and he you've gone through medical school
before these are great coverage is a great differential diagnosis absolutely
ep
events
hotbed i'd i didn't ask him about scuba diving and whether he had uh...
at whether he had done that but certainly that would be a follow-up
question that we would act
these are these are great things now let's peace apart with these things me
first of all what is a pulmonary embolism
which had pulmonary embolism you know what it ps
unexplained
so o'clock in the long
the person was sitting in mobile for a period of time which allows rumbled sis
to develop especially in the lower extremities which can then migrate up
and gets stuck in the long
you stated that his shortness of breath with sudden and so you started unpack
the whole concept of rationale and my thinking that
versus some of the other things because often times when you get a pe it
suddenly breaks off part of your of the clock suddenly breaks off and goes into
the pulmonary basketball
now you'll understate you'll start developing the language around that but
that's a great way to explain that you also mentioned congestive heart failure
now what is congestive heart
art which on the spot but i was a good differential i'm coming back into our
world seven you know
all right so congestive heart failure being basically eight at in enhanced
pulmonary vascular
in the palm area vascular system because
the heart is not able to
nearly as good injection of the blood through the periphery and so things back
up for a bride of the reasons either though
orgasm pump is well it's two-step you got valvular leakage
and it backs up into the pulmonary vasculature you increase the pressure it
you cause pulmonary edema which gives you offensive shortness of breath but as
you mentioned oftentimes that'll be accompanied by peripheral oedema because
of the heart backs up from left ventricular failure right ventricular
failure
than you actually have
summit denying your lower extremities
she doesn't according to him we haven't done the examination you so that's the
caveat here but that may be a reasonable thing to come up with uh... to uh... to
come up with in your differential and you put it lower because there were some
aspects that weren't necessarily as
consistent with that bag no's' right
so that's a that's a great way to approach the differential
i would mention obstructive sleep apnea
overhear yet
what's obstructive sleep apnea might like that that here
e
pacbell now that site so what let me just uh... unpack what you're saying
there
you're commenting on the fact that this guy woke up in the middle of the night
with shortness of breath now oftentimes people who
have obstructive sleep apnea don't actually wake up
but they have apnea episodes which means that they
stopped breathing
for a period of time and sometimes i can cause them to suddenly startle and wake
up they don't necessarily wake up short of breath but they can't
absolutely until anyone that wakes up in the middle of the night
i'm certainly thinking about sleep apnea
it's probably one of the most under diagnosed conditions in this country
i didn't know the reggie white died of it but he certainly would be pat rescue
uvic because people who have are
uh... and i don't know how it will be c was but large
body habit is certainly is a risk factor for obstructive sleep apnea
also can lead to right sided congestive heart failure so might also be connected
to one of the diagnoses that we heard early on
so keep in mind that sometimes diagnoses are completely independent of themselves
revelry talked about independent independent events
sometimes different items in your differential are actually related to
other items that you differential so we have to keep that in mind as well
by legal said feel pd in the back and now possible emphysema what is that
and why might he be at risk for them
front his
baton so
clearly he's got to look just to reiterate what you're saying
he's a smoker
long-term smoking can cause destruction and inflammation to the pulmonary
bronchus tree
andy alveolar
uh... components of it what you learn about this year and next year
uh... destruction of the albee ally is typically what we see as a mechanism
towards emphysema
which is one manifestation clinical manifestation of seo pd and certainly
can impair oxygen
exchange which would make you short of breath and destiny
and maybe he's in the early stages maybe this is just his first manifestation of
that
you know he said he has ended for breath before
but your focusing on his rest
dot keep that in mind
some people were focusing on how he presented waking up in the middle of the
night
some people are focusing on risk
both are absolutely critical as you get as you generate your differential
diagnosis
risk
drives the order often of the things in your differential diagnosis
but how u manifest
also changes the order and what you're thinking about
in a different likeness
both of the things that we need to walk in with
and as we think about observational studies tying this to what doctor grover
was talking about last week
observation als studies give us information about race
they give us information about risk factor
that contribute to different clinical case uh... disorders
so very important to trying title of this to get and question over here some
yes
back gop_ d is chronic obstructive pulmonary disease
it is the long-term manifestations of tobacco use
it can manifest through either emphysema where you have destruction of the
alveolar tissue
and impaired oxygen exchange as a result
you can also manifest as what we call chronic bronchitis where you have a
tremendous amount of inflammation
in the broncos and with mucus production which can also cause impaired oxygen
i mean
uh... oxygenation
so sorry i didn't identified annual
learn all of these concepts as you move on
so you're doing a great job building your first differential diagnosis now
the problem is is i also said
we have to start assigning probabilities to get to these different
uh... clinical manifestations of just give you an idea of what my list was
before we get started
that's right
congestive heart failure
and that the amount exacerbate shin
and i also thought about asthma which could be another
different manifestation that is not necessarily smoking related
but also uh... can contribute to airway inflammation
i didn't have obstructive sleep apnea in my differential that doesn't mean that
it's wrong to put it there
um... many people would and what you'll find is a different clinicians will
bring their different behind the scenes to their differential diagnosis
of the question is what do you do when they're all these behind seas out there
and how do we assign probabilities to the different uh... clinical
uh... entities in your differential
or sometimes we can do it by a gut feeling
based on what we know about the disease based on what we know about the patient
based on what we know about the for respects
and so here's my gut feeling differential diagnosis
i put pe at the top
i could see a jeff next
at thirty uh... and i put emphysema thirteen asthma fourth
and i tried to make it all add up to a hundred percent so it was nice to meet
so i could forty thirty twenty ten
there is at a right answer you don't know
that's just my gut feeling but what it does tell you is i didn't think that
pete was so overwhelmingly likely and i would put that at seventy percent and
everything else down at the bottom
there may be clinical conditions where you do that but keep in mind that each
one of these diagnosis
had both its
can uh... consistent features
and something that we're just kind of atypical
why wouldn't it be a pe well he said he didn't have a new leads well he'll
appear on a plane ride for five hours most people don't get a ddt_
well maybe ever
symbol that looks like
y c h f not bad
because there's you know there's some things that are consistent with a but he
doesn't have flirts from any of you
until their fingers that will sort of make you head
and these numbers are part of making
are are my manifestation of making
uh... contribute communicating the head
there a couple of other things you can do with this
so for example remember
you can combine probabilities of different events
so what is the probability that shortness of breath is due to be there p
foresee a chap
given these a particular numbers when you guys think
seventy percent
if the two are mutually independent events
meaning that they're not dependent on each other not meaning that if you happy
you are not more likely to get seja
or vice versa
because if there is that overlap remote from what we understand about the
disease and you can't combine them by adding so yes the answer to that would
be seventy percent but remember a thing in mind that provided that both don't
happen simultaneously
just as an intellectual exercise if you thought that there might be a ten
percent overlap
in the likelihood that you have both p n c h f bowing out of the same time
meaning that they are dependent and then sport
that they're both likely
uh... the it's possible that you're having both of them happen at the same
time then that you could combine the two by saying what is the likelihood that
you have either p or c h f
but it wouldn't be seventy percent
would actually be sixty percent because there's also ten percent chance
but both are happy happening simultaneously
but the good intellectual exercise to go through again the numbers art as
important as the concept that it goes down
when but to events for depend
keep in mind that in medicine
their are absolutely independent events
and their absolutely
that will be dependent and has you go through your blocks and understand the
diseases you'll get an appreciation
berwyn things are determined and when they read
so basically what we're doing is worth actually creating
prior probability
before we have done any further down the track gathering with this patient
re-affirm a couple of questions that we would ask
well before we do any further exit we can do the physical exam yet
we didn't do any real specific questioning within the week testing yet
we're generating
it prior probability remember we did that with the woman with the brc_ a
haitian that we were concerned about
we had a prior probability with her walking in
do when she was twenty years old
well this is a prior probability that's based on a number of different factors
that i doubt that i mentioned
on the other hand you can actually generated prior probability
using some tools that are out there is what don't want to demonstrate obscene
as some of the tools that might be helpful to you
so why is there are these things called clinical prediction rules
mechanical production rules are ways of using the literature and what we know
about the literature estimate s
about particular disease
and
the uh... the way that we did there are a number of them that are out there
pulmonary embolism is one of those clinical diseases that actually has a
number of different political predictions and i want to sort of show
you
what uh... what one uh... looks like
so what you have here to really think that your slides that you can use as
well
this is mad calc three counts
this is on the uh... you guys have access to this and uh... they're unknown
bura different uh...
their number of different medical calculators here
for p what you would do is you would enter in the day the for the particular
patient
and then it would give you step here in the lower right hand corner cc
so let's do that for this particular case
based on what we know right now
based on what we were going out the sixties right so we put the sixties
we also know that he's made
so we put that
and then you'll see a whole series of risk factors here
let's say we don't deal with uh... let's go down and see what he has
we know he's got the acute onset which means some that's another
word that you learn
sudden onset of this issue
we click on that
notice what's happening to the risk as we go through this
just being sixty years old and mail
and then adding acute onset of dyspnea
this risk number goes up to fifty percent
really jumps up there
and if we added that he might have been immobilized with saying this
let's say he sat
in a plane
completely comatose for five hours didn't move out what
that would probably qualify as immobilization
let's say we clicked that
you'll see that his risk of having a pe with all of this
is now sixty percent
so my gut feeling of forty percent
probably and underestimation now this is a gut feeling this is based on
spa operational stocks that are out there and putting them into a
mathematical model
you can get these things for your handheld device
you can put them on the web a lot of these are being integrated into the
electronic health record for positions
so that these
guides can be placed right at the point of care
i'd encourage you to think about these and try to explore some of these because
they were a number of these for a number of different conditions out there
but we're gonna return to this as we go through so right now
we're starting around sixty percent
as our prior probability
but you realize also that there's a number of questions here that we just
don't know the answer to the right legal fees at a fever we don't know we know
that he doesn't have a history very vascular disease
we don't know if he passed out we don't know if he's actually got one-sided
lights while
so there's more data we need to get
so let's gather
so more date
so here's some more information then i'm gonna throw at you based on this
particular case
you talk about family history find out that he actually
has had
he has a family that is that the ddt_ in the past
pretty for it
you do a physical exam on him and you find a his blood oxygen saturation is
normal on room air
so these oxygen eighty five
checkers respiratory rate at sixteen that's generally that's a little fast
but it's probably okay but
his pulse rate is a hundred and buy it now
united now that a hundred five ezell elevate we would call that eka kartik
so he's technopark
and you examine his loans as you will learn to do this year and you'll find
when you became his patients' lungs that he has crackles
ntsb's
user crackles are sort of
they sound like crackers
we've ever listen to rice crispy
that's what it sounds like a bit sounds with inspiration you would get crap that
usually indicates that there's some degree of a team up in the long some
degree of swelling in the long and as the albee a liar trying to expand
they pop open up a very easy way but enough
tough way because there's a lot of surface tension at each of you
level because of the fluid in the interstitial space
he's also got leases leases are indications of airway obstruction small
airways obstruction in the long
but you'll also notice he doesn't have a problem which means that he doesn't have
this sort of uh... inflammation in the pleural space which will learn about
and he doesn't have evidence of consolidation consolidation would give
you some clues that he might have an emo
we don't have either of those
but you also examine is like and you find that even though he didn't think it
was a swollen it absolutely is well
and you feel of any
below his knee
most of the time we should be able to feel the danes attorney but if they're
inflamed possibly because of a clock
you might feel below the knee
you get a chest x-ray that's normal
and you get the cagey in its shows that his heart's going fast but nothing's
besides that
so now what we do is we go back
to the clinical prediction
calculator and cd about entering in this data
so the additional data that will get
he not only is uh...
sixty years old and mailing it to keep this thing out and let's say he's
immobilized he was a mobile as
we now find that he's gotten lateral excellent
but that he also has leases
contracts
no notice what happens to pay attention to the number as i enter the zip
i started out with sixty percent by aditi lateral leg swelling what we're
getting really close for x seventy five percent
but this person's that p
upholding a bit
remember we're talking about as long as even though
the race
his lead
because if you've got to cut your leg you're more likely to throw that but we
have a pulmonary embolism those two are not
independent features
those who are dependent effects
so it dries it up to seven six percent but knows what happened when i clicked
on visas and practice
that number within seventy five percent of the thirty five percent
so what in your mind
must you be thinking
the presents of crackles and we use is actually make
pulmonary embolism last like
in fact pulmonary embolism the number one clinical finding in the long for p
is nothing
subtotal e normal pulmonary exam
just because you have a normal palm trees and doesn't mean you don't have a
disease
as an important consideration but keep in mind that this is a way of
quantifying
how much
dropped there is so we ever did all this data and we're now at around thirty five
percent
so turns out i was about
or a percent was pretty close to thirty five pst
there are interactional terms that are built into the mathematical model here
so if you look above the rest
and sold those interactions are built into how he calculates the factor some
which then translates to what the risks
so yes there are interaction terms between these things
and it's calc it's all done in the background
clinician you know i'm not gonna do that
and i'm certainly not to be able to look at a study be able to know how to do
that that's why these calculators to be very helpful
it'll give you an idea are we weigh off
or are we about right is this guy is
was my initial gut feeling over on target yeah
was kind of on target even when we did more data gathering
but you also get a sense
uh... why how different features increase and decrease the likelihood
which is a good learning tool
rate
so the question is of why is
smoking and wake nodding here
the answer is is that smoking and wait for actually not considered risk factors
for p
when they've looked at these studies what you might think of boy there smoker
they're more likely to have a clock
into israel
just because you're a smoker doesn't mean that you're more likely to have a
pe
now certain smokers do carry increase from body chris
if you're a young woman who smoking on or contraceptives
you already higher risk of developing a lower extremity ddt_
at is clear
but that's not necessarily what we're talking about here
over the lot big picture it doesn't contribute risk
it also could be because the studies were done but in this case is because
they're not respect
uh...
so here's the question if you are thinking that there is a nother
possibility on your differential diagnosis that is either equally or more
likely does it drive this down the absentee answers absolutely it does
and there are limits to these clinical prediction
so this is done in a vacuum their other clinical prediction rules
where you can actually have a button that says is an alternative diagnosis
equally or more likely when you do that people drop your s
because it knows that there may be other things going up this prediction will
didn't do that
station had a family history of a ddt_ but not a personal history dvd if you're
interested in what that would have done you could do it if he had a dvd in the
past
it drives up from thirty five to fifty
yet family history of some of his family with d
all these are great questions but the most important thing to keep in mind is
you don't just have to go on gut feel
at these clinical prediction rules for common diseases which are the ones that
are out there
can help you understand
the clinical manifestations of a particular disease
so what does this have to do with what we do
well keep in mind we're now
we are now at
um having completed our data gathering things were based
with the prior probability of about thirty five percent
at the station is happy
and so what we need to do you think about
do we need to get a test
because the question that should be going through your mind is the thirty
five percent high enough at allstate yahoo dot abt and got a pulmonary
embolism
we're gonna treat you as such
hopefully thirty five percent is too low for even you
to say boy i don't think that i would point to treat based on that certainly
would be low for most of the nation's we need to probably get some sort of text
so what this is a how those bridges over into diagnostic test
so here is the question what we do with this number
well if there was a test that existed that could rule in pulmonary embolism as
the diagnosis
with a hundred percent sense certainty
we would be saying that probability of this of a patient having a p
due to the
at the test is positive
is a hundred percent
and the question i would ask you is what is the stressful
what we call this test the boot stain
the gold standard generally exist for more most conditions where they're is
where works for the past week after the finding of the best will stand at the
top
uh... it may not be the best test
that we can envision
but it's the best test
that is available
and the question that i would ask is if you use the gold standard tests and you
found it
the test was positive
is the probability of an alternative diagnosis remember that a test test
that's a gold standard is only the gold standard or particular diagnosis
let's say there's another diagnosis
that you're interested in
is it zero
if the test is positive
the answer is no
because
sometimes you have two things going on
sometimes there are vents
that are related to each other dependent on each other
for sometimes you just have bad luck
as a patient
and you have both pulmonary embolism and cha_
but the most important to keep thing to keep in mind
is that we are always looking to see what the gold standard is
but we can't always used to go see
so what is that not stick testing people but not the testing
the the goal of diagnostic testing is to help us modify probabilities
we talked about how
we modify probabilities based on history taking physical exam other simple tests
complex s like the ones we're gonna talk about
will help modify probabilities as well
but they cost a lot of money
and so we need to approach argues a diagnostic tests
judicious
so in order to understand what we're looking for work in a study about
diagnostic test we need to understand
how people related items to test
really does relate instead of
the patient
uh... population were interested in
what we're really trying to use the following
a disease state
what is the disease that we're trying to diagnose
in this particular case if ur interested in another test to use
it would be the disease state would be a pulmonary embolism
intervention
would actually be the test itself so what tester we interested in his room
looking through the literature
the comparison group is not another therapy but it was in the therapeutic
questions
it's the gold standard
so you're trying to compare
a test of interest
against what is the best test that's out there
the problem with the best test that's out there is that it's frequently
infeasible
sometimes dangerous even though it's the best s so we're looking for an
alternative test that we can use i can help us with our page so that those
favoritism
and then the outcome of interest that were interested in is the performance of
the text
that's the fundamental
and you will be able to
do this
over and over again as you're looking at different studies and we've this is part
of the assignment
for two more
so let's practice
as we've seen the sixty location without heart disease is presenting with some
nonsense shortness of breath
we're considering a p
that would be our disease or our p
protest and ask us to consider is a test collabera profusion scheme
cowbell asian perfusion scan
is something that's been around for a long time
it basically
in the test a patient in hale's
or radio nuclei partner
and we see where that radio nuclei particle goals
and in addition the patient gets injected with that same radio nuclear
particle
and we see based on the blood flow
that particle goes
we take pictures
simplistic explanation but i thought you really need to know at this point
and what we're looking for is
where does the air go
that blood doesn't go
but that there's a place where the air goes that the blood doesn't go that
would likely be where o'clock would be
api
but that's what happens is that the clock obstructs blood flow to that
particular place
now the gold standard
four diagnosis of a pulmonary embolism something we call pulmonary and
geography
which is where you were actually injecting died and watching where the
blood blow goes
you see a picture of a b q scan on the top there
on the bottom is a very grainy picture of a pulmonary angiogram
just keep in mind that an angiogram
more costly
slightly more dangerous
the gold standard
but we wouldn't because it's costly and more dangerous we wouldn't offered to
all patients
because if we did that
the risk that we would in anyone who we suspect has a p
the amount of complications and cost that we would entail
would be mass
that's what we're looking to see is is of the few scan which is actually
fairly
really fairly
at not terribly dangerous
whether that would be good enough compared to the gold standard for many
of the geography
what were interested in is diagnostic performance
so that is the pico recognize the test
but before thinking about it became scandal then elation perfusion scamper
first question we have to ask
kena beat you scan actually even be used
now you will be asking this question as a clinician
but before you can even go to market
as a possible test
there's some fundamental questions about a diagnostic test
that require some definitions that you should be aware
and they thought this on to concerts accuracy and precision in order for a
test to be used
in the literature and study for possible use it needs to be accurate
and it needs to be precise or whining about it
what accuracy means at the results of the test
corresponds consistently with from result
not going to result in terms of diagnosing the disease
but the correct about
meaning that it'd be q skin if i object
the radio nuclei and i say it goes to the long
if you go to the law
and if i inhale the radio nuclei and i say he should be inhaled into the
alveolar space
it should actually be inhaled into the alveolar sticks
fundamental
but keep in mind that there is a clone of work that happens
prior to attest going to study
that requires this to happen
and there's a lot of science behind us
so needs to be accurate enemies
besides we're learning about the size twelve decision means that if you do
with over and over again on the same patient you'll get the same result
with a reliable test
the repeated values on the same sample resume results in the same down
so in the same patient you do it once you do it again five minutes later you
you five minutes later
missing uh... results actually happened
that's the preciseness
you need to have both
they're actually three different
possibilities that tend to happen
when early
phase studies are done and diagnostic tests
the first is the one that you want
want to be highly accurate and highly precise pointed out that you're good to
go
ready to go to step two and study its characteristics
however
you can have something very precise
but be completely inaccurate
that's what's represented conceptually by the bulls on where you have a lot of
different numbers there clustering all around the same area
but it's actually not doing what you think it's doing
and then there is sometimes when you have
reasonable accuracy it's all clustered around the bulls eye
but low precision
their hat you get different
answers each time you do it
so what do you do in these different situations
well the first into a single one step to your butt
the second one you gotta think about calibration
and you need to reset or maybe you need to relook at the reagents veteran vault
at a particular test itself
in the last one unfortunately you gotta start over
if you've got a bunch of if you're a test is not precise how usable could
actually be
you have to actually get the precision death
again this may seem fundamental in foundational
but there are so many things that don't make it to market for even testing
because they don't meet these criteria
important for you to keep him
once you make it past that first phase then you can decide
diagnostic performance it what the diagnostic performances the o of the
pico for diagnostic tests
and so fundamentally
i would ask you to think about two things
any good diagnostic study does this
they take a well-defined group of people
who are at risk for a particular condition
a whole population of them and they expose them to
the experimental tests
and the gold st
everyone in the study needs to have both
and if you compare the test results
experimental tests
and the gold standard
keep in mind you don't want that patient population to be
everyone having the disease a hunter percent of them having the disease
you need to have a fair number
of people who don't have the disease in order to test
the test characteristics
well that's the fundamental premise of any good diagnostic study and you'll be
able to recognize he's
what we can do is determine the strength of the association
between the study results of the diagnostic test
of interest and the gold standard missiles he just comparing the two how
well do they compare against each other
the strength of all of that statistical significance is the degree of
correlation begin the accuracy or not yet received the test results all the
two different tests that are on in this particular set
clinical significance is another factor we're not going to talk about that
right now
well what we need to do is focus on statistical significance
so before we break i'm just going to
present to you with the way that i'm gonna ask you
to think about
and represent that data
from a diagnostic study that does exactly what
what i'd just out
a diagnostic study you are looking at
the
performance of the test of interest
and the gold standard he's y
t
better out there to buy two table
to be able to represent
how those the study participants a sort themselves based on how the test of
interested
and how the gold standard label
across the top you always
you always uh... the columns are represented by those that tested
positive
for the disease based on the gold standard medical center
work theoretically calling a hundred-percent
therefore each identified those in the population who have the disease
and those that test negative by the gold standard
will be in the second call
but all of these populations
in the study
there will be some of those that also tested positive based on the
experimental test you're interested
and some that test lead
and sometimes they're going to agree
with what the gold standard says
such as inbox a and boxy
sometimes they're going to disagree
with what the gold standard set
based on box b and boxy
for simplicity safe keep in mind that we arent we are
assuming that the gold standard is a hundred percent
so we're just gonna assume that whatever the gold standard said is true
and we're comparing it against test of interest
each of these boxes have different names that are going to come get introduced to
you
does that work
disease are are labeled correctly by experimental tasks
as having the disease based on the gold standard are called true positives
their inbox it
those that are correctly labelled as not having the disease by the experimental
test relative to the gold standard are considered true naked
those that are
falsely labeled as having the ditsy
based on the tax
but they actually build because the gold standard sent me one
are called false positives
and those that are falsely labeled at not having the disease
when they actually do
are called false names
the standard nomenclature
gotta remember it
fairly straightforward false positives false names
these areas of agreement these are the areas of disagreement
what we're going to do no
is picked up
with our
figuring out how we use this to define test characteristics
so let's take a five minute break
and then we will come back and talk about
the test characteristics better rise from this to my teeth