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so d. m. i found actually d. set picture quite quite
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inspiring systems fate what an artist's uh feels uh
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uh when uh she has a a a vein troubles the deep thing troubles is
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and uh and and you see the the the degree of saw friends and uh uh especially
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uh uh in the treatment of this kind of fumble this is a very standardise and
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very advanced uh something similar happens in the in
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the portal vein of jesus and despotic area
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but we we don't know exactly what's the consequence are in this in this area
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and we are absolutely not advanced in terms of standardisation of treatment and even
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less uh in terms of onto cooperation so what i wanted to
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a good tool would you worked three points the mechanism veterans of
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a new a class of rocks the affects of these uh
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direct alright i've ah to quite blunt especially in patients presenting with
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a chronic advance lever disease and uh i'm finally some
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words about uh the indication if there is one about monitoring
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and uh which dog is good for which patients
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we have our uh free directing beaters or factor twenty we have one any better off from being
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and the acting the final part of the cascade indy
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are currently i'm used for the prevention of stroke
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for the treatment of venus from where embolism for the prevention of a trim waist one is after
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me or heap are purposely not thing to do would portal vein proposes the real novelty
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is that uh tends to set a a degree of a of a safety is that we
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can uh antagonists this we can do with with a a ten a uh um yeah
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to um uh antidote switches uh and excellent we can utilise that we get front with an antibody
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and uh in uh probably the next month we we have a a
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a new one which is syrup around talk which is a
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a general uh an antidote for orange quadrants that we are uh
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currently uh using of course not for vitamin k. antagonist
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so the evidence that uh these trucks are good calms for or
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from a big registration studies use here dear
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dear dear uh it being housings of
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patience and what what it is interesting is that in terms of uh
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of us for core systemic timberlake events compared to vitamin
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k. antagonist when you want to quadrants are better
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okay in terms of building a the pieces
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to this is to be differentiated because yeah you see that
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uh there are two oh uh drunks which are pick
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seven and it took someone which are clearly better so less bleeding then on to vitamin k. into drugs
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that we get from the river oaks of and where this evidence is not based
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clear so if we um focus on a efficacy and
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safety outcomes we can clearly see that's a docks
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are better in terms of a more logic stroke they are better
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in terms of uh inter crying out hemorrhage but interestingly
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uh and this is relevant to particular eleven for
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us as far as gastrointestinal bleeding is concerned
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probably dogs are more dangerous than uh on t. vitamin k.
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uh these are data from a registration study what to use uh in in the
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real word in the real word you see that if we uh compare
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seventy thousand two more than fifty thousand patients treated with dogs or
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we'd harder and requirements in terms of g. i. bleeding
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there is no difference so we can conclude okay there is no problem however if we have a closer look
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uh to this data we see that the reading crystals of major j. believing
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that are associated with that be that front plus twenty seven or
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revoke seven plus forty percent but not for the other ones there are
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some risk groups which are patients over for a seventy five
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patients presenting liver dysfunction uh impaired the party functional we've come
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back to this end concomitant use often to brackets
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and finally uh h. two receptor antagonists or p. p.
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i. appears to be protective against uh against building
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and if we compare uh uh relate to each other the
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different uh dogs in terms of risk of gastrointestinal bleeding
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you see that uh and i'm not going to details but
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compared to the other um docks optics upon seems
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to be better than the be the trend and the bigger trend seems to be better than remarks about
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so taking together this uh data shows us that uh that be that
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trend and vivid rocks upon in terms also major baiting overall
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are the same as vitamin k. antagonist while at big seven hundred and that talks about her better
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major ga bleeding is uh is higher would that be that front
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ends weaver oxygen but not too with with the other two
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and it's major inter cranial buildings is lower with all the locks compared
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which is a a and t. vitamin k. uh um
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medications once again in the real word in the
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state of more than forty thousand patients uh
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this is our confirming that a a major bleeding events uh ochre less
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frequently in a in a the locks than in a war firming
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hear the difference is not really a significant inter cranial
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bleeding of course less uh but you see that
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yeah it should be eating uh uh at least for
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uh the b. that final course uh more frequently
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so while it occurs where uh those it's does it do so
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in the upper g. i. tract it's a a pack teach also disease in
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the lord your track to see that uh the vertical are um
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the article or bleeding but interestingly if you look at uh the
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percentage of patients who has to have to be osprey televised uh as you can see
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that this percent is is a fifty percent impatient with docks a while it
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is a a much higher in patients with conti vitamin k. and also the duration
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of uh or speech energy hospital decision is screw shorter in patients treated with
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a dog so clearly a an advantage these study is a excluded as the vast
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majority of the other studies is excluded patients with zeros is so we have
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to look into the studies to find out patients with zeros disease or a survey
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uh all of a a gastrointestinal bleeding after endoscopy each interventions and uh
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uh we see that in general uh the incidence of
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bleeding is higher in patients treated weights or suffering
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compared with docks this is not a statistically significant but it's
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always it's always the saying trends and uh if we
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look closer to an indication which we found we find
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that uh endoscopy should various allegation is also included
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meaning that she or a a a sorority patients must be included
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and and and treated with with the uh with dogs disease uh
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fifty versus a a fifty four and you see that uh
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there is here also a a march of uh uh security
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if you want to but this is not a significant
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but this is something that fits that happens so the frequent situation is uh that we use
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dogs uh when you we assume that the reason only the disease for a very common
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uh conditions that i'm not related to advance chronic liver disease and this is a rare situation
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where we know that our patients are a um a lever sick and we
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treat conditions that are associated with this disease support having trouble this arbitrary
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of course patients with advanced liver disease can also be treated in these
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in these indications but in the studies this patients have been excluded
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what are the effects of the works uh in these patients we
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have to uh scenarios on the left side you see the
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changes that we observe in patients with stumbles is primary most
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places is disturbed cooperation is disturbed fibre analysis is disturbed
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we have to take into account this and on the other hand former co kinetic
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um uh situations are different and i'm i'm going to show you an example
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and a farmer coding on each uh aspects as also
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different because there wasn't a an increased or did
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might be an increase plus my plasma level of this uh drugs but data are very um
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very uh controversial you see here the levels of
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a river rock seven impatient had to subject
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patient with mild or moderate the political impairment meaning child a in child you and you
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see as expected that's the levels of a a plus money the rocks about our higher if
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the lever is stick in that action of a uni beating tiny is a um
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is more is higher and it probably the pro probing time is higher here so expected for iraq's about
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for a for a box upon we have the country you see you see
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here that there is no difference in concentration but uh if uh
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if you see uh the data in moderate departing payment you see that
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uh in the head the subject uh uh the the the level
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orthodox someone is higher dan in a a lever such a subject so we don't know exactly what
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the mechanism uh are but we we we we cannot conclude uh with with generally that uh
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zero to patients have higher level of these drops another point of course is drug
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induced liver injury it is expected enough to one percent of the patients
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it's less frequent than with low will occur are way temperance or vitamin k. antagonists it's
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more able to sell were then course static injury and it is more frequent
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with river rocks about dan would that be that front or uh peaks
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which is relevant what is relevant for us is that uh we
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are using some some dry conservative patients in when we
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decide to want to cooperate we have to uh draw attention to the fact that especially with the big upfront
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and in some cases wait it talks about we have to call c. there i read option
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when we use a beta blockers when we use stay things and when we use um
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a thankless boring or probably most in our transplanted patients
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one of course the in only only really really uh zero to but
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keep in mind that uh uh this can be an issue
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in another issue can be lever injury you see that's a d. u. um attitude should be different
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that electron is the lesser a safe drought in this uh uh context you see that
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uh in levels of cutting the clearance less than a a fifty meters
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per minutes we should decrees any level it's a on of less
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than thirty meters of uh uh per minutes you have to decrease
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the those two fifty percent whichever also wanna know doc seven
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and also here to to fifty percent and consider that basically in patients with a crafting enough
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not threatening clearance of less than than a fifteen
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it's basically a no go for four blocks
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the data uh about the safety as if it and efficacy
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patients with it's uh s. roses are very rare
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you see here all the studies that are available low number of patients a little uh or
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short a duration of a followup major breaking occurring
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in a proportion that he's actually uh
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in the same range and is the proportion observed in anti vitamin k. a.
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or a low wicker way to point but remember that these studies a
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retrospective and then not have not been designed for for a process this and
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what what is of course a problem for us is that the
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the the proportion of security patients child see is uh
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zeroing the majority of the study and fifteen percent only only in one in one study so
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uh did the data uh showing that major bleeding uh
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easel covering more or less uh with the
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same frequency as a as a the other on
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squadrons must be taking very very cautiously
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um it is interesting to see that uh in a in the context of truth in a strong one policeman uh
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in patients presenting with uh elevated serum i mean the
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try a trans i mean is is um docks
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our our uh um i think the study where um prescribed much more frequently
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then uh uh on t. vitamin k. e. uh medications it's not clear
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why but uh it's also interesting to see that in intensive care
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uh uh the treatment of uh i'm actually things from what
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is is that really really uh done with dogs
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in contrast emergency care station this is the most the use of the
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drug probably because uh uh with dogs you reach a a very
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rapidly uh uh the the right speech a plasma levels and uh
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this is the distribution of the use of our uh products
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a deluxe entities probably what we also do does more uh more or less at fifty percent to rocks
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about forty percent the big seven weeks upon and uh a bit uh docks upon and the bigotry
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in the there are two other considerations that i would like just to mention and it is that the locks
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in not all basically uh it can be used but they can cut a accounts that there is
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a a a large volume of distribution and basically what
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you should consider is that in patients with a
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b. m. my of more than forty or more than one hundred and twenty children body weight
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you should not use a a dogs uh and gore
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other for a vitamin k. antagonists and uh
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this is a concern was all in patients who are a little weight
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impatience of less than sixty kilograms you should reduce
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uh those at least for a big seven and the docks about but there are no recommendations were all fisher recommendation in
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this area but consider that a frequently uh see what the
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patients presents a a sock opinion and this should be
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uh uh taking into account the locks may be good for security patients
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because they have some and if i brought each uh um
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action you see that they contributes in an animal model
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to uh improve into t. i. dysfunction they are associated with last fibrosis as a
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see that uh by quantification of us i'll have a small monsieur acting
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ends they can lower puerto pressure although this is a a um
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this uh use uh mm it's in statistically
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significant but it's it's uh uh uh
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only only point four percent and this is not a good uh only for
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the lever the antibiotic effect is uh uh was observed on carpet fibres
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results of sort of i don't go into details up except on is uh
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also in a beating fibrosis in pulmonary fibre blessed in that we
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get found a decreases in you know in v. form or the five
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boroughs is of the longs in people so it it appears
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to be a general uh and if i brought each effect and uh
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i'm going to a close my presentation with the last part which
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is uh important because you cannot money toward your d. d. d. the
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efficacy of the tree to me docks however you should know
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that uh especially locks upon is increasing uh do here in our uh
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value of your patients but you can use the n. r. as as up
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as i'm a marker all funky cooperation in that case and that that
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electron is prolonged in the g. d. yeah a p. t. t.
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so uh i just taking two into account decent this is another a way of seeing these things you see
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that uh a pity and the input from in time are increased but uh you see that uh
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pro and speak levels are overlapping here for that you
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get from any particular for a pick someone so
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if you measure the the the the plasma level of the straps you cannot
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the say where where you are if you are in a in a in a a
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in an area where you are um therapeutic rather choppy twentieth efficient or or not
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and uh you see again the very larger interval of concentration
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in a in a in class model for all the for
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a dogs and you see here that when you know
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uh the concentration is increasing the un t. ten a action
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is uh is uh not not morning or so
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you do the she messages that you can you you
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cannot use plasma levels to uh evaluate the
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efficacy so basically the recommendation that we have for the
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use of dogs anybody's are that you should evaluate
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your function test before starting and consider that there are practically no data in shied see patients
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you should monitor liver function during the treatment especially the elderly patients or patients taking other um
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people to talk such a drunk forty you should adapt the doors according to the renal function
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and you know that uh security patients are have a very variable a kidney function
00:19:18
and consider stop docks in case of a step of uh was position for drug related it but the
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toxicity tried a is a is a green area
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a caution is needed for child be patients
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and for child see patients um caution is is is recommended
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uh i think we very rarely treat these patients and if we do so then
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that we limit it's at a c. ten or or or or eleven
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uh and this is my i think almost three seconds last slide how do you select
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the right the ox considering the patients profile uh when the release euros is
00:20:01
is the reason i risk of gastrointestinal bleeding in this
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does not include uh viruses that includes uh
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a risk of bleeding in vices which is the dimension
00:20:13
and the right size but not viruses percent uh
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it's better to use a a big seven or the bigots running reduced those if there is a
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high risk of general bleeding then saying kings but you can use all the docks upon
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if you have a uh an advanced liver disease child be then a core or
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maybe it's good to avoid river rock seven for a a a decrees uh in a renal function
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yes then uh fifty meters per minutes curtain clearance then you should
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decrease or consider decreasing the dot's en it's uh if
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for the patients is not fully compliant or once only one uh p. per day then the
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river oaks upon or it looks upon should be should be selected so into close
00:21:04
uh i would like to to to conclude by saying that currently available data
00:21:08
so just the dogs are safe and effective uh in the presence of mind
00:21:13
to more the right advance chronic liver disease so opt to try it
00:21:17
b. b. nine or c. ten data are needed in stage see patients
00:21:23
in addition to liver function we i figured right interaction asian be
00:21:27
yeah my should be considered before starting this treatment docks may
00:21:33
have also on to fibre optic treatment so they could be indicated
00:21:36
in the um uh five brodie diseases including zeros is
00:21:40
in serum levels are not sufficient for monitoring
00:21:45
our soap here and i thank you for your attention
00:21:54
hannah lisa mm thank you very much and uh it's really a difficult topic at the end because
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i always ask myself what to do when we have a patient
00:22:06
with a child c. is on the way to respond transplantation
00:22:09
bean develop those are nice for the winter mosey beneath not
00:22:13
complete that we want to preserve the papacy or the
00:22:18
a conference and you because you you need to receive a transplant then
00:22:22
we need to treat then we cannot use the works then um
00:22:28
mostly this patient have a good reason features you so they
00:22:31
are not ideal candidate anyway what do you do personally
00:22:38
it's it's it's a very complex situation might personalised experience but i think we
00:22:43
can share its or maybe blowing i dunno bits this safest order
00:22:50
easiest to to to to use triage are a little more like are
00:22:54
we temperance uh if you have a ah unacceptable kidney function
00:23:02
uh i'm speaking about really zero to patients the the patients on
00:23:06
the least uh with uh because of h. c. c.
00:23:09
are different they can be use with dogs they can be treated with dogs but they re us robotics are are
00:23:15
are really difficult and uh i think personally i tend to to switch to um
00:23:22
to look for what happens but they have to to to to inject it
00:23:28
and uh and this is not that easy and you have a two c.
00:23:31
d.'s patients very frequently because if they uh develop it but we'll syndrome
00:23:36
or any kind of like you have have as we have seen this morning this is a this is a major problem because then you should
00:23:43
go for for a non fraction it it forms a whimpering and this is this is
00:23:49
this is complicated so my personal preference is a fax
00:23:55
repairing or clicks on is that ordering your
00:24:02
more freedom to tie traded those those with low manipulates freezes this page and often have a
00:24:08
if not to mention the low platelet counts soul how how
00:24:13
lowell you'll there to goal with uh and columns because most of
00:24:19
these at least anybody we cannot prescribe when you want
00:24:22
to call warrants a bit direct and problems for a portal
00:24:26
in trouble just because that existed only for uh
00:24:29
prevention most rock and for our and we'll probably embolism so the second question is
00:24:36
in case use it for both of interim balls is do you think that this
00:24:39
same those is the recommended because really the the others are life threatening conditions
00:24:46
portal interim was used as a that was said not always is a life threatening condition um so
00:24:51
it might not even be directly their functions so it is really needed that would give the
00:24:56
full dawes or we might maybe after one mansell words will be those that the nobody no the
00:25:02
present so but if you have your personal opinion it would be nice to hear it
00:25:10
mm that i that was mentioning it and that has been always be
00:25:15
that paschal from boxes near the call for and that then
00:25:20
then what we do all is a trial of low weight a
00:25:24
plane and if he doesn't work we go for tapes
00:25:30
that that's what it back to you and uh
00:25:40
to complete a form thing from e. d. but really if it's lacking in pregnancy we
00:25:52
don't have data so for the history and the companions this don't you see
00:25:58
well it ended with vitamin k. it's always the question it favourite so let's
00:26:01
say in the past week like the switch to the l. x.
00:26:05
it it the data is it clear what i bought probably because it wasn't like
00:26:09
it's coming on the market or a cox our dates on the market
00:26:13
uh the problem it let me know this disturbing you
00:26:17
can smash and that makes it more complicated in
00:26:20
in levers in in in surrogate patients i'll try that c. i. c. patients had to say
00:26:27
i'm a strong believer in that part but i mean we say
00:26:32
single pill for all patients except for the extremities i'm in body weight
00:26:38
and just for us real something we most frankly see as a as a country indication that
00:26:47
you know what it would be yeah at that site apology patients so we had this this this
00:26:56
is not a with with that out with chemotherapy i bought that even with vitamin k.
00:27:01
i mean that that thing is like family well kinetic so that it's like a little more
00:27:06
like away hap right so so even after intake and you have a complication i mean
00:27:11
four two forty six hours late at the half life is already
00:27:14
gone so all the discussions on and you got someone is
00:27:18
bullying and you don't even like to too late so he
00:27:22
you have even with vitamin k. antagonistic allow that matches
00:27:26
and and he i mean until the patient in the hospital have like ten what gone and you're dealing
00:27:31
with something we all know follicle wait happens and we don't just discussed that inside the as well
00:27:38
so so my fault it's it's in favour wrap up the problem is ah
00:27:43
there are no they they nail recommendation for the sake of
00:27:46
the industry and and ah e. for legal issue
00:27:53
or any other questions
00:27:58
i'd together with the patient to use dog and we have we have patient
00:28:03
mean don't even mean waiting list on the drawn transplantation these very important
00:28:08
to discuss with patient the pros and cons and to have a return
00:28:11
documentation stating that the patient wants to go and accept the reason
00:28:18
and to discuss interdisciplinary also with the code except the weight is because for instance
00:28:23
um is this your reduced at that issue with a patient that was
00:28:27
on the rocks one and it was called the unexpectedly for transplant
00:28:31
and then they could not antagonist so that's why now for these
00:28:34
very specific cases we do not longer use them so it's
00:28:38
i think it's very important to be very open and close by and go to the discussion does unknown an unknown yeah yeah
00:28:46
o. e. k. o. e. c. d. how flat it's so short and we don't think about well michael way
00:28:55
hap right so so even in tight see personally i would vote for deluxe except the special situations
00:29:04
four
00:29:05
as a few relation and pulmonary embolism you might stop if you'd was the first occurrence
00:29:12
in the the situation as disappeared if you the second instance you goal long life
00:29:19
if you use a for portables rumbles which is your time you knew how long should be should be taking
00:29:25
yeah and the calculation because for instance for oracle wait a plane
00:29:30
initially we tended to so expand it a one to two months after the disappearance of the
00:29:36
traumas but we had a thirty four percent of recorders so now we have we baiting
00:29:42
how long whether you this is the yeah i don't have any as
00:29:49
but you know that's i was it on to the any answer but my
00:29:52
attitude or how well you don't monitor them soul you save a
00:30:01
physician consultations u. c. v. in our measurements every week so in the
00:30:06
end i'm i don't know if it is really more expensive but
00:30:11
okay okay you know right
00:30:20
want to come to your to your question i think that uh if you identify
00:30:25
risk factor for puerto having troubles isn't is risk factor is to present
00:30:31
as you mentioned so a trouble free yeah oh or or or
00:30:35
or or whatever the including in my opinions you roses
00:30:39
is that on the field factor then uh probably to make sense to continue
00:30:45
if you have a local factor that is eliminated or issue have a a point of
00:30:51
income poses due to c. m. v. infection it should seem infection or or
00:30:55
or something that you can you can see and you can demonstrate that it's over the risk is over
00:31:02
then my opinion it's justified to stop a treat and but in zeros
00:31:07
this if we accept the two roses approach for multi condition
00:31:11
then i would tends to continue although it's true that we have
00:31:14
for this to seventy percent of cases of spontaneous resolution
00:31:19
of composes which would not justify articulation
00:31:24
i think that the the more importation is paradoxically to see whether
00:31:31
and the well once can improve zeros is it they improved because we will
00:31:35
use them all over and when we land in every single situation
00:31:40
if this is not the case they need a little bit of to to gonna
00:31:43
catch say so it has to have an impact and probably orgies and
00:31:50
and uh the the the the studies of a recovery like that was in these as i think
00:31:57
has not been depicted it typically has been said that many more people will do the same
00:32:03
as the the the gunfire with the night but it's it's not and so um
00:32:09
we need such information on a block it's occupations you always good with opera genders could be
00:32:19
oh
00:32:23
i don't do it's a always i. e.
00:32:32
yeah i get that workers is in the home
00:32:40
because the corporations states
00:32:43
what it did to your study would factor seven demonstrate that if you change corporation you don't improve anything
00:32:49
in terms of of of outcome of bleeding right
00:32:58
then no we we should then we should
00:33:06
yeah and if we have if you have viruses are introduced me to brokers in then you want to go with it
00:33:19
ah
00:33:24
uh_huh
00:33:27
there are various questions
00:33:37
i just increase the flow dramatically i do create up it imposes but
00:33:45
the change in the speed the plough with but that locus about probably to circle
00:33:52
then you have other effects of that will that be a a farewell and it'll be
00:34:01
the product of like ox right you can you can modify the things i
00:34:09
okay i think each we stop here thank you very much to all i
00:34:14
would like to say two things the first one is that uh
00:34:18
we have the we have the opera which is the most important thing up arrow and it occasional
00:34:24
uh events are supported by the industry so thank you very much to uh your support we
00:34:30
could not do this if uh you were not here
00:34:33
so thank you very much um for the
00:34:37
people who need star here um participation so uh
00:34:42
uh documents so just take one copy
00:34:47
thank you very much for your for your contribution rupert to see patients so you will

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