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twitjournalclub Fi (@fidouglas) will be chairing & dealing with any technical issues, and Natalie
(@silv24) will be presenting the paper. ^fd #twitjc -7:53 PM
twitjournalclub Key points - is this paper valid, what are the results and are the results valid
outside of the context of the paper #twitjc -7:54 PM
peds_id_doc @twitjournalclub Hmmm...the CASP toolkit is a start, but I have extra thoughts for
the budding researchers among ppl here... #Twitjc -7:54 PM
fidouglas @peds_id_doc Hold that thought - sounds interesting, but not sure there's the time/space
here at the mo...! #twitjc -7:55 PM
twitjournalclub Both @fidouglas & @silv24 are new to this so please bear with us ^ns #twitjc -7:55
PM
peds_id_doc @fidouglas there'll be time I'm sure...If a suitable place pops up I'll slip something in.
#ooermissus #Twitjc -7:56 PM
rodedun good luck to @twitjournalclub @fidouglas @silv24 for an excellent idea you guys are
amazing #twitjc -7:56 PM
parkerflash RT @rodedun: good luck to @twitjournalclub @fidouglas @silv24 for an excellent idea
you guys are amazing #twitjc -7:56 PM
silv24 RT @rodedun: good luck to @twitjournalclub @fidouglas @silv24 for an excellent idea you
guys are amazing #twitjc -7:56 PM
behrouzn RT @rodedun: good luck to @twitjournalclub @fidouglas @silv24 for an excellent idea
you guys are amazing #twitJC -7:57 PM
tobyhillman Toby checking in for #twitjc Resp SpR. Eating, and trying to converse with wife, but
will follow attentively... -7:57 PM
fidouglas RT @rodedun: good luck to @twitjournalclub @fidouglas @silv24 for an excellent idea
you guys are amazing #twitjc -7:57 PM
fidouglas @peds_id_doc Jolly good! I'm just looking to keep things reasonable on topic this evening
- gonna be easy to get sidetracked! #twitjc -7:58 PM
peds_id_doc @fidouglas if I need to I'll throw my thoughts out separately at the end ;-) #Twitjc -
7:58 PM
anaestheticdoc ooooo ooooo is the tweetchat working.evening all! very impressed #twitjc -7:58 PM
aj0610 Hello to #twitjc; AJ, Pharmacology grad, 4th yr medic at Aberdeen -7:59 PM
peds_id_doc Peds ID fellow from Cambridge UK, currently in Upstate NY doing, err, the fellowship
#Twitjc -8:00 PM
DrDLittle Tweetchat working well. I'm David, currently a teaching fellow, soon to be Radiology
trainee #Twitjc -8:00 PM
iamdoctord Richard CT2 Medicine in Northern Ireland saying hi too #twitjc -8:00 PM
drbrown1970 Russell Brown, GP in Sussex (will be mostly lurking tonight) #twitjc -8:00 PM
Shazmo Charlotte, 1st yr med student. May have to dash soon but will catch up later (: #twitjc -8:00
PM
JoBrodie #twitjc Jo, science info officer for @DiabetesUK keen on improving critical appraisal skills
for medical papers -8:00 PM
silv24 Hello all - Natalie Silvey, first year doctor currently working in gastroenterology #twitjc -8:00
PM
parkerflash Nice one! I'm back. Final year med student, soon to be academic foundation trainee.
Love a bit of SIRS. #twitjc -8:01 PM
medicscott Scott Berwick, 1st Year Grad-entry Medical Student. Degree in Biomedical Science.
#twitjc -8:01 PM
MargoJMilne Hi I'm a non-medic with a degree in Health Studies / Human Biology #twitjc -8:01
PM
EasternDoc Hello all, I'm Simon, FY1 working in East Anglia #twitjc -8:01 PM
dtwatkin Evening all. David Watkin, paediatrics trainee in the West Midlands #twitjc -8:02 PM
alexwintermute Hi, Alex here, grad entry medicine pre-fresher and HCA #Twitjc -8:02 PM
MedEdHelen Helen Morant, ex anaesthetist, now working at BMJ in online learning. (I once knew
this paper well - its been about 5 years...) #TwitJC -8:02 PM
ABLocalBargains #aberdeen RT @aj0610 -Hello to #twitjc; AJ, Pharmacology grad, 4th yr medic
at Aberdeen -8:02 PM
benazevedo 3rd year med student, Tulane University in New Orleans #twitJC -8:02 PM
chrisking01 Hey I'm Chris, hospital pharmacist and soon to be medical student #twitjc -8:02 PM
behrouzn Hi everyone!! Behrouz, hoping to start medicine next year. Just reading tonight. #twitJC -
8:02 PM
Iwanttobeamedic Non medic Undergrad - shall be mostly lurking this evening #twitjc #twitjc -
8:02 PM
rodedun Hello all Rebecca, final year med student at UCL, listening from the bath. Lol. #twitjc -8:03
PM
Chestcracker Hello everyone. I'm Norman, a cardiac surgeon in Sheffield. This is really exciting to
be on a world first #twitjc -8:03 PM
northern_doctor I'm Mark - ST3 in Geris & stroke; working as a TRF in North East #twitjc -8:03
PM
fidouglas Hello! I'm Fi - Med student at Cambridge, going into 3rd year this autumn - I'll be posting
under @twitjournalclub too this evening. #twitjc -8:04 PM
amreeeves Hello! Andy Reeves, 3rd year student at Leicester, just observing tonight :) #twitJC -
8:04 PM
FayetheGEP Evening, I'm Faye, biomedical sciences grad now 1st year medical student at Barts. Will
just be taking a back seat and watching! #twitjc -8:05 PM
JimHigginson #twitjc Hi, I'm Jim, Surgical trainee, about to jack it all in for dentistry as a stepping
stone to maxfax. -8:05 PM
twitjournalclub Thank you all for the introductions - great to have so many people joining in ^ns
#twitjc -8:05 PM
DrElfy I have no interest in joining in (pub quiz beckons////) - just wanted to see if this would work ;-
) #twitjc -8:05 PM
twitjournalclub Right, people can introduce themselves as they arrive. For anyone unclear about
the paper, brief intro here: http://wp.me/p1BLwH-u #twitjc -8:07 PM
doseofnuxvomica hi, sarah, london, fy2 and soon-to-be psych trainee, currently eportfolio-ing like
crazy for sign-off. but will be watching #twitjc :) -8:08 PM
themattmak #twitjc So, how does one start discussing? I'm limited by being on iPhone in a car
(passenger!) and dot have tweet chat! -8:08 PM
twitjournalclub The framework we're using for discussion can be found here:
http://bit.ly/kBwEPV ^fd #twitjc -8:08 PM
siobhanfarmer Hi. Siobhan, Public Health StR in the NW. May be only half watching #twitjc
tonight but will try to keep up :-) -8:09 PM
JimHigginson @alexwintermute: Pure Hardcore. Except that I'm scared of it all tonight and crying
for my mum. #twitjc -8:09 PM
twitjournalclub The first topic to be discussed this evening: Did the study ask a clearly-focused
question? #twitjc -8:09 PM
johnoliverdunn Evening all-John-Oliver, Anaesthetics SpR, Wessex, UK. I'm on labour ward so
may be distracted... #twitJC -8:10 PM
peds_id_doc I think we can safely say the question was good - also limited to a pt population that
seemed to make sense #Twitjc -8:11 PM
dralindsay #Twitjc Alistair Lindsay - JournalScan editor for @Heart_BMJ and Cardiologist -8:11
PM
northern_doctor Clearly focused question: Yes, I think so. Complex variables & outcomes, but well
defined and explained. #twitjc -8:12 PM
peds_id_doc One of the problems with any study is enrolling pts who might screw up the results by
having conditions that confuse things #Twitjc -8:12 PM
JoBrodie Curious why it's named "Goal directed therapy" w'out specif naming what the goal or
therapy is ;) Could be for any old thing hehe #twitjc -8:12 PM
DrDLittle @twitjournalclub I guess it did ask a focused Q, 'does goal directed therapy improve
outcome in terms of mortality?' #Twitjc -8:12 PM
peds_id_doc @JoBrodie That was one of my issues - had to delve into the paper to figure out what
that meant! #Twitjc -8:13 PM
DrDLittle @JoBrodie agreed, seems to be slightly unrelated to the main theme! #Twitjc -8:13 PM
peds_id_doc @JoBrodie I guess it should be "goal directed versus uber-goal directed" #Twitjc -8:13
PM
JoBrodie I agree w @DrDLittle - I think it was a focused question. Seemed to me (non-expert) that
population was defined too. #twitjc -8:13 PM
MedEdHelen very clearly focussed question - but how useful a question is it? #TwitJC -8:13 PM
northern_doctor @JoBrodie Trying to be succinct, I guess. They do define it in the text, but it's not
straightforward. #twitjc -8:13 PM
dtwatkin I felt a little ignorant not knowing what goal-directed therapy was! Explains itself further
in! #twitjc -8:14 PM
silv24 Well-defined population with clear exclusion criteria, clear description of the intervention and
outcomes measured #twitjc -8:14 PM
anaestheticdoc @peds_id_doc @JoBrodie think the goals do become obvious once you read the
paper. and on the flow chart. #twitjc -8:14 PM
basmahassan #Twitjc oh hello.. Basma.. Ct1 in the mess of a london hospital. -8:14 PM
iamdoctord Fair question, 'early goal-directed therapy before admission to the intensive care unit',
but is admission to ITU same as mortality? #twitjc -8:14 PM
northern_doctor @JoBrodie This also raises an issue about how easy it would be to transfer
protocols to practice & educate staff about it! #twitjc -8:14 PM
parkerflash @peds_id_doc the abstract does outline what they meant by "goal directed therapy".
It's more or less the headline of the paper. #twitjc -8:15 PM
JoBrodie @peds_id_doc I like to think all therapies are directed towards some goal or other ;) just
an odd phrase, by itelf. OK in context #twitjc -8:15 PM
peds_id_doc @amcunningham @peds_id_doc @jobrodie more than that - the existing standard
used guidelines, they were looking at more specific ones #Twitjc -8:15 PM
drgrumble Doesn't this paper just show that you need to get on a treat and not leave things till later?
#TwitJC -8:15 PM
silv24 @iamdoctord all were admitted to ICU - the mortality was looked at in-hospital not just in the
ICU #twitjc -8:15 PM
DrDLittle @anaestheticdoc @peds_id_doc @JoBrodie perhaps, but it is by no means clear what goal
directed therapy is for a non-expert #Twitjc -8:15 PM
MedEdHelen "goal directed" is a method of care. in kind, it is like studying if "directly observed
thearpy" works #TwitJC -8:15 PM
MargoJMilne @KimMKendall Hey, have a look at #twitjc hashtag..idea is to discuss a medical paper
every Sun evening -8:16 PM
twitjournalclub So we think it was focussed in terms of population studied. What about the
interventions given? Were they sufficiently clear? ^fd #twitjc -8:16 PM
iamdoctord The flow chart is useful guide for interventions #twitjc -8:16 PM
drgrumble Treating very sick people promptly is better than delaying. Surprise, surprise. #TwitJC -
8:16 PM
JoBrodie @MedEdHelen Aha, does that account for extra ScvO2 monitoring bit then? I think that
was the main diff, & haematocrit (...googling!) #twitjc -8:17 PM
MedEdHelen In some ways, I think this is a quality improvement paper. It's about how we do care.
#TwitJC -8:17 PM
parkerflash yes - a picture speaks a thousand words here. RT @iamdoctord: The flow chart is useful
guide for interventions #twitjc -8:17 PM
peds_id_doc @twitjournalclub interventions were VERY well laid out. Even as a non-intensivist it
made sense and I could follow the plan #Twitjc -8:17 PM
DrDLittle @twitjournalclub yes, the flowcharts were very clear about interventions #Twitjc -8:17 PM
kevfrost @silv24 #twitjc so doesnt necessarily apply to patients not admitted to ICU? -8:17 PM
amcunningham RT @drgrumble: Treating very sick people promptly is better than delaying.
Surprise, surprise. #TwitJC -8:17 PM
anaestheticdoc not all therapies have a goal. Can be much fairly arbitrary when to start and
commence some treatments. #twitjc -8:17 PM
peds_id_doc @drgrumble I agree - I have my own thoughts on this from the IRB perspective...
#Twitjc -8:17 PM
fidouglas They seem to define set physiological parameters which determine what treatment is
initiated. Which seems fairly clear-cut to me. #twitjc -8:17 PM
northern_doctor Interventions were well defined, but with the caveat of being subject to variable
clinical decisions (eg. prescribing abx) #twitjc -8:17 PM
themattmak #twitjc I think the word 'early' is important here, as it most certainly improved
outcomes hence protocols now with door-to-needle times -8:17 PM
peds_id_doc @kevfrost @silv24 I doubt anyone with SIRS won't float through the ICU at least for a
day... #Twitjc -8:18 PM
alexwintermute As a non-expert, it wasn't that defined for me. It gives no method of how it could
be implemented. (our ward does send to ITU) #Twitjc -8:18 PM
northern_doctor However, the documentation of which interventions were made in each group
was good #twitjc -8:18 PM
silv24 I think the interventions were very clear - the flowcharts in the paper made it easy to follow the
treatment of both groups #twitjc -8:18 PM
amcunningham @peds_id_doc @drgrumble why might goaldirected therapy not have worked?
Was there equipoise here? #TwitJC -8:19 PM
northern_doctor "@fidouglas: They define set physiological parameters which determine what
treatment is initiated." - Agreed. Important point. #twitjc -8:19 PM
tobyhillman @MedEdHelen to a degree, I don't think there was anything too revolutionary in the
rx, more in the rigid mode of delivery #twitjc -8:19 PM
peds_id_doc @fidouglas also, transfusing blood to get a set hematocrit isn't always the norm,
especially with a view to maximise O2 #Twitjc -8:19 PM
MedEdHelen remember this paper is nearly 10 years old - it defined a lot of the way we are expected
to "do care" today. #TwitJC -8:19 PM
silv24 Agree with @fidouglas - the physiological parameters are set out well in the paper - easy to
follow #twitjc -8:20 PM
AandE_SHO #twitjc early treatment should be paramount in treatment of sepsis, provided you have
a focus and no compromising differential diagnosis -8:20 PM
anaestheticdoc @tobyhillman @MedEdHelen thats exactly the beauty of this paper, doing simple
things quickly early and well #twitjc -8:20 PM
chrisking01 @twitjournalclub believe the paper does have a well focused q, with clear specific
protocols. Goal directed therapy; explained well #twitjc -8:20 PM
Onisillos #TwitJC manuscript editor for the lancet. Hope I can keep up -8:20 PM
rodedun l.o.v.e. the flowchart. but that might be because i'm a tad simple. #twitjc -8:20 PM
drgrumble @amcunningham @peds_id_do Could be the wrong goal. What about that recent
research from Africa in children? Fluids worse. #TwitJC -8:20 PM
peds_id_doc @amcunningham @drgrumble it just struck me that the study was ideal versus less
than ideal (standard) care. #Twitjc -8:21 PM
northern_doctor @peds_id_doc I've never seen this done, but then again I'm not an intensivist...
#twitjc -8:21 PM
aj0610 As a student and thus non-expert I thought the flowchart made things really clear #twitjc -
8:21 PM
tobyhillman @AandE_SHO was that learned independently of this paper - it has had a massive
influence since publication #twitjc -8:21 PM
iamdoctord The protocol is defined quite specifically in the 'methods section', no illusion as to what
outcomes were expected... #twitjc -8:21 PM
JoBrodie I keep having to look up Wikipedia for the big words :) Heard of some, can't remember
what they are. Also the flowcharts were good. #twitjc -8:21 PM
twitjournalclub Final point in this section - would we agree that the outcomes were clearly
defined? ^fd #twitjc -8:22 PM
themattmak @MedEdHelen totally agree, we take a lot of the stuff they do in the paper for granted,
but this was surprising news for many #twitjc -8:22 PM
peds_id_doc @northern_doctor we would transfuse to maximise crit...but only with a view to the
crit, not a central O2 measurement. #Twitjc -8:22 PM
fidouglas @aj0610 Agree with you there - made things quite clear for me, and I've got very limited
clinical experience. #twitjc -8:22 PM
kevfrost @MedEdHelen #twitjc absolutely, this has heavilly influenced our sepsis protocol -8:22 PM
DrDLittle @AandE_SHO agreed! There is good evidence for that, mortality increasing with each
hour without abx etc etc #Twitjc -8:22 PM
MedEdHelen @amcunningham I think the point was to prove that non goal directed therapy was
definitely bad. #TwitJC -8:23 PM
JimHigginson @twitjournalclub APACHE II scores is clear enough for me. I don't like using
physiological parameters though, too indirect. #twitjc -8:23 PM
drgrumble Didn't both groups end up with essentially the same treatment. Just one was speedier
than the other. #TwitJC -8:23 PM
doctorblogs RT @MedEdHelen: remember this paper is nearly 10years old- it defined a lot of the
way we are expected to "do care" today #TwitJC -8:24 PM
simonpeteryoung #TwitJC a lot of physiological targets in ICM based on close ties with cardiac
anaesthesia, and the pulmonary artery catheter -8:24 PM
peds_id_doc @drgrumble @amcunningham depends how much fluid :-P #Twitjc -8:24 PM
theMedicator #twitjc interventions were clear and concise, I think that was one of the factors.. -
8:24 PM
anaestheticdoc @drgrumble not really as a Vo2 was never managed in the non intervention group.
#twitjc -8:24 PM
themattmak @twitjournalclub definitely. Mortality at different set days is a good end point to study
#twitjc -8:24 PM
drgrumble The interventions were simple but delivering them promptly is not always so easy in
practice. #TwitJC -8:24 PM
iamdoctord As a non-intensivist, APACHE scores can be confusing, but I understand what they try
to identify... #twitjc -8:25 PM
peds_id_doc @drgrumble No, the goal-directed group were given blood, more narrow BP range,
dobutamine and ventilated per protocol... #Twitjc -8:25 PM
JoBrodie By outcome measures does everyone mean the mmHg / %O2 etc measurements., or death?
Obviously I feel silly for asking :) #twitjc -8:25 PM
fidouglas @drgrumble One of the docs here would probably know more, but GDT group had scvO2,
SaO2, Crit etc. monitored as well... #twitjc -8:26 PM
JimHigginson @JoBrodie both for the purposes of the research, but clearly the latter is more
important to patients! #twitjc -8:26 PM
peds_id_doc @JoBrodie all measurements! I guess the argument is by optimising the early goals,
the end goal (mortality) is better #Twitjc -8:26 PM
drgrumble @peds_id_doc Was it the difference in treatment that mattered or the speed of delivery?
#TwitJC -8:26 PM
northern_doctor @iamdoctord Same, but as long as we have early access to someone who
understands them then the patient's heading in right direction #twitjc -8:26 PM
TWSY 3PQ then: In patients with sepsis, does early 'assertive' intervention aiming for physiological
targets improve survival #twitjc -8:26 PM
drbrown1970 @fidouglas @drgrumble Heh, that's what you get from GP's skimming papers...
#twitjc -8:27 PM
JoBrodie @JimHigginson Haha, yes indeed :) #twitjc -8:27 PM
peds_id_doc @drgrumble maybe both - I'm sure some in the control group never got
blood/ventilated when they would have in the GDT group #Twitjc -8:27 PM
twitjournalclub Section Two: Was this an RCT? Why was this approach used? Is it suitable? ^fd
#twitjc -8:27 PM
MedEdHelen @JoBrodie they discuss a few outcome measures. more interesting to ask if it matters
if you have a great pO2 if you're dead. #TwitJC -8:27 PM
themattmak #twitjc although, it's interesting every pt had a CVP line before getting to ITU. That
still doesn't happen in today's world... -8:27 PM
AandE_SHO @DrDLittle #twitjc many variables tho, pt concerned, staff you have (competency) ...
all been there, nothing is textbook unfortunately -8:28 PM
TWSY In terms of importance of the paper, are we agreed that it was an important question? #twitjc -
8:28 PM
simonpeteryoung #TwitJC remember CVP very dependent on many things (RV compliance, IPPV,
etc) - many confounders -8:28 PM
aj0610 Technically was an RCT but changed too many things so hard to interpret imho #twitjc -8:28
PM
iamdoctord Certainly optimising numbers is one thing, whether they live or die seems an
appropriate primary outcome measure... #twitjc -8:28 PM
peds_id_doc The RCT bit worries me...just how do you get "written informed consent" from
someone in SIRS...? Truly no influence..? #Twitjc -8:28 PM
simonpeteryoung #TwitJC lactate & SCVO2 prob make more sense as targets -8:28 PM
tobyhillman @themattmak context v v important, note art line and cvp in the Ed for each patient -
am sure we will get to this... #twitjc -8:29 PM
AandE_SHO @tobyhillman #twitjc tbh u guys have more info than me, my adobe reader crashed.
besides isnt this why we audit and have NICE -8:29 PM
JoBrodie Is it safe to assume that people in the state of sepsis / septic shock are REALLY ILL and...
aha just seen @peds_id_doc's Q #twitjc -8:29 PM
kevfrost @twitjournalclub #twitjc were patient subgroups excluded because they couldnt consent? -
8:29 PM
anaestheticdoc you can argue whether cvp is an acurate measure of rv filling, but it was one of the
goals which worked. #twitjc -8:29 PM
peds_id_doc As a study plan, the RCT approach is ideal to answer this question...but speaking as a
clinical researcher...seems off key #Twitjc -8:29 PM
iamdoctord I concur RT @peds_id_doc: The RCT bit worries me...just how do you get "written
informed consent" from someone in SIRS...? #twitjc -8:29 PM
alexscott292 @simonpeteryoung Is this Rivers or have you got a linky to this paper? #TwitJC -8:29
PM
JoBrodie @peds_id_doc Yes I wondered, maybe they asked family members and I didn't spot it.
#twitjc -8:30 PM
JimHigginson @themattmak should it happen? I thought CVP lines from A&E are more likely to
introduce infection than ICU ones? #twitjc -8:30 PM
northern_doctor RCT? Yes, although difficult to achieve full blinding. #twitjc -8:30 PM
anaestheticdoc @JimHigginson @themattmak not if they are insterted as part of the sepsis care
bundle and done properly. #twitjc -8:31 PM
aj0610 @northern_doctor Does state ICU staff blind as to which treatment initially received but obv
initial tx not blind #twitjc -8:31 PM
peds_id_doc @JoBrodie they reference the Helsinki declaration. I think that even allows no
consent under emergency situations (must be approved) #Twitjc -8:31 PM
amcunningham @aj0610 why only technically RCT? Good that happened in 1 centre so
randomization at level of individual- increased power #TwitJC -8:31 PM
MedEdHelen It took them 3 years to enrol 263 patients - I imagine they struggled with consent for a
lot of patients. #TwitJC -8:31 PM
silv24 Paper clearly describes an RCT (partially blinded) and think it was appropriate ...interesting
issues with recruiting sick patients #twitjc -8:31 PM
northern_doctor The study was designed to be clinically relevant, so they should be applauded for
that. #twitjc -8:31 PM
dtwatkin RT @peds_id_doc: The RCT bit worries me...just how do you get "written informed
consent" from someone in SIRS...? Truly no influence..? #Twitjc -8:31 PM
peds_id_doc @aj0610 @northern_doctor In our hospital we know every med/order done in ER.
You NEED to know what meds they got there! #Twitjc -8:32 PM
fidouglas @kevfrost Exclusion criteria incl DNR/Advanced directives that restricted the protocol.
Asume not all patients conscious? #twitjc -8:32 PM
drbrown1970 @JoBrodie @peds_id_doc Where the rules any different re consent a decade ago? I
don't think so, but I could be wrong. #twitjc -8:32 PM
TWSY @twitjournalclub You are asking 'Was RCT the right design to answer this question?'. Yes
because it is asking about an intervention #twitjc -8:32 PM
kevfrost @northern_doctor #twitjc you dont need blinding for it to be a rct, (unblind vs single blind
vs double blind) -8:32 PM
fidouglas @anaestheticdoc Once they'd be transferred to a different team after 6 hours, it was
blinded. Before that, no. #twitjc -8:32 PM
JimHigginson @anaestheticdoc @themattmak fair enough - I've only worked in places with A&Es
too busy to do it properly. That obv. needs to change #twitjc -8:33 PM
northern_doctor ...but that wasn't the point of the study. It's about judging the efficacy of a bundle
of care based on physiological principles #twitjc -8:33 PM
aj0610 @amcunningham Suppose I just thought too many variables to know which made the
difference #twitjc -8:33 PM
northern_doctor @kevfrost Agree, but not sure it could really have been as blind as they claim as
all treating docs would have access to notes #twitjc -8:33 PM
anaestheticdoc @northern_doctor @aj0610 dont need to identify which one made a difference. it
is a care bundle #twitjc -8:33 PM
JoBrodie @twitjournalclub Is this 'goal directed therapy' now normally done in all / most cases of
sepsis, where appropriate? Is it standard? #twitjc -8:33 PM
theMedicator #twitjc surely randomised controlled was the only option as questions regarding
interventions were being asked, non? -8:34 PM
silv24 Blinding: staff in the ITU who took over care didn't know which group the patient had been in
for the first 6 hours of treatment #twitjc -8:34 PM
peds_id_doc @drbrown1970 @JoBrodie don't know if rules were diff...and any local IRB can be
more strict if they want. Many are. #Twitjc -8:34 PM
tobyhillman @northern_doctor is the conclusion not that the full bundle required to produce the
difference? #twitjc -8:34 PM
MedEdHelen Full on double blinded RCT ? no. I can't think of how they could do better to answer
the question & care for patients ethically #TwitJC -8:34 PM
themattmak #twitjc not having this study as double-blinded doesn't reduce the quality of its
findings -8:34 PM
northern_doctor @anaestheticdoc Agree - just made that point, but had to split into 2 tweets - obv
wasn't fast enough in posting ;-) #twitjc -8:34 PM
amcunningham RT @kevfrost: @northern_doctor #twitjc you dont need blinding for it to be a rct,
(unblind vs single blind vs double blind) -8:35 PM
JimHigginson @MedEdHelen that's the paradox of clinical science though - same with surgery,
can't double blind a surgeon! #twitjc -8:35 PM
DrDLittle @twitjournalclub Seemed to be appropriately random with an equal split between groups
#Twitjc -8:35 PM
anaestheticdoc i know they say the itu were blinded, but the first thing you do on arrival to ITU is
read patients notes #twitjc -8:35 PM
tobyhillman RT @northern_doctor: @anaestheticdoc Agree - just made that point, but had to split
into 2 tweets - obv wasn't fast enough in posting ;-) #twitjc -8:35 PM
northern_doctor To clarify: Agree 100% blinding not necessary, just saying it prob wasn't as clear
as claimed in paper! #twitjc -8:35 PM
twitjournalclub Sorry to hurry things along - we've got ten questions to get through, and the
questions get more interesting later on! ^fd #twitjc -8:35 PM
parkerflash RT @anaestheticdoc: i know they say the itu were blinded, but the first thing you do on
arrival to ITU is read patients notes #twitjc -8:35 PM
MedEdHelen ah look, 3 tweets saying the same thing #we're all right. #TwitJC -8:36 PM
silv24 RT @MedEdHelen: Full on double blinded RCT ? no. I cant think of how they could do better
to answer the question & care for patients #twitjc -8:36 PM
peds_id_doc MT @northern_doctor:...but that wasnt the point of the study. Its about judging the
efficacy of a bundle of care based on physiology #Twitjc -8:36 PM
EasternDoc @silv24 but were they truly blinded? Surely they could have easily found out from the
patient's notes prior to ITU admission? #twitJC -8:36 PM
northern_doctor "@anaestheticdoc: they say the itu were blinded, but the first thing you do on
arrival to ITU is read patients notes" <-- Exactly! #twitjc -8:36 PM
Manjit49 RT @MedEdHelen: It took them 3 years to enrol 263 patients - I imagine they struggled
with consent for a lot of patients. #TwitJC -8:36 PM
medicscott Randomisation was by non-investigator choosing envelope which contained one of the
protocols. Best way to do things? #twitjc -8:37 PM
Manjit49 RT @MedEdHelen: Full on double blinded RCT ? no. I can't think of how they could do
better to answer the question & care for patients ethically #TwitJC -8:37 PM
iamdoctord The control and intervention populations from base-line characteristics appear
similar... #twitjc -8:37 PM
kevfrost @EasternDoc were the patients blind and doctors not eg single blind rct? #twitjc -8:37 PM
drgrumble 8.7 percent were excluded or did not consent to participate. Not bad. #TwitJC -8:37 PM
MedEdHelen Appropriate allocation? yes, I think so, again, can't think of a way to do it better in the
circumstances. #TwitJC -8:38 PM
TWSY @twitjournalclub Randomisation ok I think, but gold standard computer randomisation via
telephone call? #twitjc -8:38 PM
northern_doctor Allocation to groups was random & appropriately done. Groups were matched so
no obv. confounding factors. Analysis was ITT = good. #twitjc -8:38 PM
twitjournalclub Continuing the issue of blinding, Section 4: Were participants, staff & study
personnel "blind" to participants' study group? ^fd #twitjc -8:39 PM
drgrumble @medicscott There have been examples of the 'right' envelope being chosen. #TwitJC -
8:39 PM
iamdoctord Interestingly similar prop. of patients not making it to the 6 hour window, were these
patients so sick that intervention futile? #twitjc -8:39 PM
peds_id_doc Question re: blinding tho. If you knew your pt was control, wouldn't you work
HARDER on them in the ICU... (reverse bias) #Twitjc -8:39 PM
JoBrodie I'm collecting the hashtagged tweets here for reviewing later, this is moving quickly and
I've lots to learn! http://is.gd/HAYA0V #twitjc -8:39 PM
aj0610 @TWSY Guess that is difficult when it's such a time-crucial study #twitjc -8:39 PM
silv24 Allocation and randomisation good - especially for a single centre study #twitjc -8:39 PM
fidouglas @peds_id_doc Surely you want to get a positive result so you'll work harder on the
'intervention' group? #twitJC -8:40 PM
drgrumble @DrDLittle Somebody thought they might have struggled to get consent but that
suggests not. Many studies are much worse. #TwitJC -8:40 PM
TWSY @aj0610 Is done in EDs, e.g. CRASH II, 3CPO and 3Mg #twitjc -8:40 PM
simonpeteryoung #TwitJC could quibble over sepsis vs SIRS but in the real world difficult to tease
out in early stages -8:40 PM
amcunningham @peds_id_doc ha! True. Hard to say impact of blinding #TwitJC -8:40 PM
chrisking01 @twitjournalclub Think the paper requires more clarification as to the extent of
blinding and how this was achieved... #twitjc -8:40 PM
DrDLittle Does it say if patients were blinded? May have missed that. (although most probably too
sick to know ;) ) #Twitjc -8:41 PM
drgrumble @JoBrodie There have been tales of envelopes held up to the light or one being thicker
than the other. #TwitJC -8:41 PM
TWSY @twitjournalclub Blinding inadequate, but ok to be pragmatic when you have to be #twitjc -
8:41 PM
peds_id_doc @fidouglas depends...ICU versus ER rivalry. Not to be ignored ;-) #Twitjc -8:41 PM
CdrHBiscuitIII @peds_id_doc Knowing they're a control would make you feel they were more
likely to develop complications, it would bias research. #Twitjc -8:41 PM
silv24 RT @TWSY: @twitjournalclub Blinding inadequate, but ok to be pragmatic when you have to
be #twitjc -8:41 PM
iamdoctord RT @anaestheticdoc: Secton 4 not convinced staff were blinded #twitjc -8:42 PM
fidouglas @TWSY How would you go about improving the blinding? How can docs not know what
they're doing to their patients?! #twitjc -8:42 PM
peds_id_doc @drgrumble @DrDLittle I routinely average 50% refusal for safe, already
approved/tested vaccine studies. *rolls eyes* #Twitjc -8:42 PM
northern_doctor @DrDLittle Imagine it would be difficult to blind the patients if they're getting
central venous catheters inserted! ;-) #twitjc -8:42 PM
peds_id_doc @northern_doctor @DrDLittle I think everyone got a CVC - difference was what u did
with it. #Twitjc -8:42 PM
doctorpreneur Sorry to miss #twitjc today -> will try to join next time! @twitjournalclub -8:43 PM
TWSY @fidouglas Not sure you can improve the blinding, hence need to be pragmatic #twitjc -8:43
PM
DrDLittle @peds_id_doc @drgrumble @DrDLittle wow! That's interesting! They did pretty well
then #Twitjc -8:43 PM
fidouglas @doctorpreneur Stick around - we've got a while to go! #twitjc -8:43 PM
peds_id_doc @TWSY @twitjournalclub I agree - all things considered, I think they did the best
they could with blinding #Twitjc -8:43 PM
drgrumble I doubt the blinding was a big issue. And the end point was hard. #TwitJC -8:43 PM
MedEdHelen @doctorpreneur @twitjournalclub join in! we're still on blinding. Not yet got to the
meaty bits... #TwitJC -8:44 PM
Charlotte_C89 On the train home, reading posts from #twitjc Really interesting. -8:44 PM
twitjournalclub Section 5: Were all participants who began the trial accounted for at its
conclusion? #twitjc -8:44 PM
AandE_SHO agree with blinding unless done in separate departments/locations. ?no #twitjc -8:45
PM
benazevedo Agreed. RT @chrisking01:Think the paper requires more clarification as to the extent
of blinding and how this was achieved... #twitJC -8:45 PM
kevfrost @DrDLittle #twitjc how would a patient know, unless it was explicitly stated or they were
an ICU doc, which they were receiving? -8:45 PM
drgrumble What are the meaty bits. Is it that oxygen delivery is key or that early intervention is what
matters? #TwitJC -8:45 PM
adriamarilla #twitjc perhaps the paper needs to clarify more in order to say if it was blind or not.. -
8:45 PM
JoBrodie @twitjournalclub I thought they were pretty clear about what happened to each patient -
seemed OK to my untutored eyes. #twitjc -8:45 PM
TWSY @twitjournalclub Accounted for yes, and included in intention to treat analysis too...very
important... #twitjc -8:46 PM
northern_doctor "@tobyhillman: @northern_doctor is the conclusion not that the full bundle
required to produce the difference?" Absolutely! #twitjc -8:46 PM
medicscott I liked the round up of 'drop-outs'. Seemed to be fairly equal between groups, suggesting
it was randomised well. #twitjc -8:46 PM
DrDLittle RT @medicscott: I liked the round up of drop-outs. Seemed to be fairly equal between
groups, suggesting it was randomised well. #Twitjc -8:47 PM
northern_doctor I think we're all agree that elements of the design are not academically perfect,
but well-balanced against clinical pragmatism! #twitjc -8:47 PM
MedEdHelen Section 5: Yes. We know what happened to all the patients who entered the study.
#TwitJC -8:47 PM
DrDLittle RT @northern_doctor: I think were all agree that elements of the design are not
academically perfect, but well-balanced #Twitjc -8:48 PM
twitjournalclub Hang on. I've dropped a Tweet somewhere. ^fd #twitjc -8:48 PM
amcunningham #twitjc its kind of disappointing that a lot more written about results than nature
of intervention and control. -8:48 PM
silv24 Intention-to-treat in their analysis - seems to have been done well #twitjc -8:48 PM
peds_id_doc @TWSY @twitjournalclub yes, ITT analysis is the closest to real world you'll get...
#Twitjc -8:48 PM
northern_doctor Were all patients accounted for? Yes, no arguments from me there. #twitjc -8:48
PM
iamdoctord RT @silv24: Intention-to-treat in their analysis - seems to have been done well #twitjc -
8:49 PM
northern_doctor "@silv24: Intention-to-treat in their analysis - seems to have been done well" <--
Important for clinical implications #twitjc -8:49 PM
twitjournalclub Another question on balance between groups - Were participants in all groups
followed up & their data collected in the same way? ^fd #twitjc -8:50 PM
MedEdHelen @amcunningham I think that's because its more about process of care than the
interventions themselves. #TwitJC -8:50 PM
peds_id_doc @twitjournalclub Looks like data acquisition was the same...again, hard endpoints of
mortality helps #Twitjc -8:51 PM
amcunningham #twitjc hmm wondering if overtreatment of controls in ICU might have been factor
in less good outcomes -8:51 PM
northern_doctor "@twitjournalclub: Were participants in all groups followed up & their data
collected in the same way?" <-- Yes #twitjc -8:51 PM
peds_id_doc @anaestheticdoc ITT is important because in real world you may decide to treat a pt
with X but the actual treatment may change... #Twitjc -8:51 PM
adriamarilla No doubt seems that all the patients accounted for.. #twitjc -8:51 PM
Assidens RT @rodedun: good luck to @twitjournalclub @fidouglas @silv24 for an excellent idea you
guys are amazing #twitjc -8:52 PM
amcunningham @MedEdHelen yes but we don't have much idea what was process of care in
standard group #TwitJC -8:52 PM
peds_id_doc @anaestheticdoc no use if a med is 100% effective if only 50% of pts take it. End result
is only 50% improvement. #Twitjc -8:52 PM
benazevedo @peds_id_doc @TWSY @twitjournalclub Why? (still learning about ITT) #twitJC -
8:52 PM
twitjournalclub Little bit of stats now. Section 7: Did the study have enough participants to
minimise the play of chance? #twitjc -8:53 PM
northern_doctor ITT analysis more representative of real clinical practice rather than an "ideal"
research world #twitjc -8:53 PM
themattmak @amcunningham I think there's the possibility that even the non-intervention ones
received better than 'standard' therapy #Twitjc -8:53 PM
drgrumble @peds_id_doc The figures for ventilation and inotropes in the two groups were similar.
#TwitJC -8:53 PM
MedEdHelen What he said RT @northern_doctor ITT analysis more representative of real clinical
practice rather than an "ideal" research world #TwitJC -8:54 PM
DrDLittle @themattmak @amcunningham How could you have prevented that? #Twitjc -8:54 PM
fidouglas Re: Q7 - they did a provisional test of power of analysis beforehand. See pp1370. #twitjc -
8:54 PM
AandE_SHO #twitjc what reference point is more relevant, ED or ICU? early treatment will
generally start in ED.. -8:55 PM
MedEdHelen @peds_id_doc they've done it for you in "statistical analysis" section #TwitJC -8:55
PM
drgrumble @peds_id_doc I think timing might just be the thing that really mattered - as we know it
does for antibiotics. #TwitJC -8:55 PM
aj0610 If under-powered study, sure error bars would overlap and p value insignificant - not so in
this case #twitjc -8:55 PM
anaestheticdoc yes just calculated it and the trial was adequately powered......... honest. #twitjc -
8:55 PM
fidouglas @amcunningham More important than P values are power. No statistician myself, but
they've talked about power values = good I guess?? #twitjc -8:56 PM
amcunningham @peds_id_doc @twitjournalclub yes they did a power calculation #TwitJC -8:56
PM
aj0610 @drgrumble @peds_id_doc That's what I meant about too many changes - is it all necessary
or did just one bit make the difference? #twitjc -8:56 PM
peds_id_doc @MedEdHelen *re-reads methods section* why, so they did. And it looks awesome.
Carry on, carry on. #Twitjc -8:56 PM
chrisking01 @twitjournalclub can anyone break down the stats analysis for a stats novice? #twitjc -
8:56 PM
fidouglas @aj0610 It's way more complex than that. Depends on type of error bar. SD? SE? 95% CI?
#twitjc -8:56 PM
MedEdHelen @anaestheticdoc please show your workings in 140 characters or less. #TwitJC -8:56
PM
JoBrodie RT @chrisking01: @twitjournalclub can anyone break down the stats analysis for a stats
novice? #twitjc -8:57 PM
silv24 I will say that my knowledge on stats is poor at best but looks ok!! #twitjc -8:57 PM
amcunningham @fidouglas well if the study was underpowered we'd have to winder about nonsig
results #TwitJC -8:57 PM
Assidens @twitjournalclub @fidouglas @silv24 #twitjc" sorry not able to participate, however
reading along with interest, well done to all involved. -8:57 PM
drgrumble @peds_id_doc But they did detect a difference so it really is irrelevant now. #TwitJC -
8:58 PM
amcunningham @fidouglas but since calculation done, and differences seem unlikely to be due to
chance - happy #TwitJC -8:58 PM
TWSY @AandE_SHO I think it about goal direction vs clinican's discretion, presumably not goal
directed not though that isn't made clear #twitjc -8:59 PM
twitjournalclub So we've established there's (probably) adequate power & there is definitely
significance. Or something like that. *headspins* ^fd #TwitJC -8:59 PM
peds_id_doc @drgrumble hopefully, but suggests they didn't miss anything. Also explains their
total numbers of enrolled pts. #Twitjc -8:59 PM
twitjournalclub Much more descriptive Section 8 which we've partly answered already: How are
the results presented and what is the main result? #twitjc -9:00 PM
MedEdHelen the "statistical analysis" section in methods is quite good at saying how and why they
did the stats they did. #TwitJC -9:00 PM
amcunningham @fidouglas was the study overpowered? Why 15% reduction in mortality? Might
have been ok with less in trial? #TwitJC -9:00 PM
drgrumble @twitjournalclub This power thing is irrelevant because P=0.009 #TwitJC -9:00 PM
northern_doctor "@twitjournalclub: theres adequate power & there is definitely significance." <--
Significance in primary outcomes, importantly #twitjc -9:01 PM
fidouglas @amcunningham P values not that small though, to be fair. In my mind, anyway, 0.01 =
"Definitely significant". #twitjc -9:02 PM
MedEdHelen Is this the bit where I say I would have liked more graphs? #TwitJC -9:02 PM
drgrumble @northern_doctor Even if they had not had adequate power the result would still have
been highly significant. #TwitJC -9:02 PM
peds_id_doc @amcunningham @fidouglas Good question -they had a DSMB - could an interim
analysis have stopped it sooner with sig results? #Twitjc -9:02 PM
northern_doctor Secondary outcomes are interesting, but main implication is from primary
outcome - reduced mortality #twitjc -9:02 PM
JoBrodie @DrDLittle Me too. I always say that, learn some, then forget instantly! They did Students,
x2 and Wilcoxon's. Must have been busy! #twitjc -9:03 PM
amcunningham #TwitJC they actually had 33% relative reduction in mortality so should it have
been stopped earlier? -9:03 PM
fidouglas @MedEdHelen Agree. I looked at those tables and thought, "Oh, I shalln't be reading
those"!! #twitjc -9:03 PM
anaestheticdoc @TWSY you keep asking the question, you work it out! #twitjc -9:03 PM
northern_doctor @drgrumble Yes, but they wouldn't have known that at point of study design.
More significant than expected! #twitjc -9:04 PM
fidouglas @TWSY Are you talking about different ways of presenting risk reductions? NNT v RRR v
ARR? #twitjc -9:04 PM
tobyhillman RT @TWSY: NNT to save one life? #twitjc -9:04 PM
drgrumble @amcunningham Not if we are still arguing about whether or not the result is
meaningful. #TwitJC -9:04 PM
simonpeteryoung @drgrumble @twitjournalclub ah but then the non-sig results are left
vulnerable #TwitJC -9:04 PM
silv24 The headline figure as I said in the blog - is the reduction in in mortality - the primary outcome
of the study #twitjc -9:04 PM
drgrumble @northern_doctor True but it is not a question to ask at the end unless they had found
no difference. #TwitJC -9:04 PM
fidouglas If 16% ARR in in-hospital mortality, that's a NNT of almost exactly 6. (No calculator to
hand) #twitjc -9:05 PM
DrDLittle RT @silv24: The headline figure as I said in the blog - is the reduction in in mortality - the
primary outcome of the study #Twitjc -9:05 PM
anaestheticdoc that low, blood hell. effective then. NNT of 6 #twitjc -9:05 PM
amcunningham @drgrumble we're not still arguing about whether result meaningful #TwitJC -
9:05 PM
twitjournalclub So aside from reduced mortality, which other results are particularly important?
^fd #twitjc -9:06 PM
northern_doctor @drgrumble Yes, I agree. Was referring to adequate power in study design.
#twitjc -9:07 PM
silv24 RT @anaestheticdoc: that low, blood hell. effective then. NNT of 6 #twitjc -9:07 PM
aj0610 Length of hosp stay obv an issue re: cost etc #twitjc -9:07 PM
drgrumble @amcunningham Well I'm not either but if the trial had stopped earlier the P value
would not have been so low #TwitJC -9:07 PM
benazevedo There was room to spared... RT @drgrumble: @amcunningham if the trial had stopped
earlier the P value would not have been so low #twitJC -9:09 PM
chrisking01 everyone's on about costs these days. Patients with early goal directed therapy spent
less time in hospital #twitjc -9:09 PM
fidouglas @aj0610 Yup, agree with that, especially when money is such a consideration in
healthcare. Keepin' politicians happy 'n that! #twitjc -9:09 PM
simonpeteryoung #TwitJC alive or dead at a specific time period - quality measures, longevity, etc
but ridiculously hard to measure -9:10 PM
JoBrodie ~31% patients had diabetes - would that info be from their general medical records or
tested from contemporaneous BG tests? #twitjc -9:10 PM
tobyhillman @chrisking01 they also used a whole load more blood #twitjc -9:10 PM
TWSY @twitjournalclub other important results would normally include bad outcomes from
intervention as a balance to the benefit #twitjc -9:10 PM
aj0610 @JoBrodie Well DM increases sepsis risk so high number of diabetics expected #twitjc -9:10
PM
medicscott Standard therapy stayed 'significantly longer' in hospital. Important for cost & risk of
nosicomial infections. #twitjc -9:11 PM
TWSY So, important question and answer (NNT = 6), valid up to a point......applicable though?
#twitjc -9:11 PM
kevfrost NNT 6.25 if you use their percentages (derived from Kapler-Meier), lower from raw data RT
@aj0610 I got 6.25 for in hosp mortality #twitjc -9:11 PM
peds_id_doc I would have liked to see days in ICU as an outcome...did I miss that? Didn't see it.
#Twitjc -9:11 PM
northern_doctor @fidouglas @aj0610 Cost less important for me. More about increased patient
risk with unnecessary bed days (HAIs etc) #twitjc -9:11 PM
drgrumble @northern_doctor A lot of people die so there are a lot who can be saved. Not like
aspirin given to fit people. #TwitJC -9:11 PM
MedEdHelen length of stay isn't just about cost. few patients prefer a longer length of stay. #TwitJC
-9:11 PM
twitjournalclub So section 9 is: How precise are these results? Again, we've discussed a bit about
this already, but what are your thoughts? ^fd #twitjc -9:11 PM
fidouglas @northern_doctor @aj0610 Yup. spending time in hospital is just generally bad... #twitjc
-9:12 PM
JoBrodie @aj0610 I wonder if the percentage of pwd even higher, with undiagnosed people, but I
expect they'd do glucose testing anyway. #twitjc -9:12 PM
aj0610 @northern_doctor @fidouglas definitely agree, better all round to get out of hosp asap!
#twitjc -9:12 PM
chrisking01 @tobyhillman reduced mechanical ventilation in early goal directed therapy. ? reduced
risk of vent assoc pneumonia? #twitjc -9:13 PM
JoBrodie @twitjournalclub Looking up to see exactly what 'precise' means in this context :) #twitjc -
9:13 PM
amcunningham #TwitJC have we resolved question of whether there should have been interim
analysis? -9:13 PM
anaestheticdoc length of stay can again be a bit of a soft outcome. may just have kicked them out
quicker. #twitjc -9:13 PM
silv24 Does the paper mention is there were any adverse events due to the early-goal directed
therapy? #twitjc -9:13 PM
TWSY @twitjournalclub Precision: no NNT in paper so no confidence interval for the NNT either. It
could be worked out though #twitjc -9:14 PM
JoBrodie @amcunningham There were two of them weren't there? I'm not sufficiently able to
comment much tbh. #twitjc -9:14 PM
northern_doctor "@drgrumble: Lots of people die so a lot can be saved." <-- Wonder how many
other interventions can claim NNT of 6 for mortality! #twitjc -9:14 PM
DrDLittle @silv24 Dont remember seeing it.There can't be that many potential adverse effects
anyway #Twitjc -9:15 PM
TWSY @silv24 Good question. They don't seem to ask themselves this question specifically #twitjc -
9:15 PM
fidouglas @silv24 What are you doing differently that could potentially lead to problems? #twitjc -
9:15 PM
chrisking01 @silv24 valid point. can't remember coming across it, then again very easy to focus on
what you want to read! #twitjc -9:15 PM
anaestheticdoc RT @drgrumble: Lots of people die so a lot can be saved." Wonder how many other
interventions can claim NNT of 6 for mortality! #twitjc -9:15 PM
drgrumble @DrDLittle If more had needed ventilating that would have had potential problems. But
there was no difference. #TwitJC -9:16 PM
amcunningham @JoBrodie @silv24 you're right! It would have been good to see data from interim
analyses #TwitJC -9:16 PM
drgrumble @anaestheticdoc Lots. Antibiotics in this context for a start. #TwitJC -9:16 PM
kevfrost @silv24 It doesn't appear that they were looking for any, if there were any to be had?
#twitjc -9:17 PM
northern_doctor Don't think patients harmed were mentioned, but hard to imagine there would be
adverse effects of intervention arm #twitjc -9:17 PM
Manjit49 RT @MedEdHelen: length of stay isn't just about cost. few patients prefer a longer length
of stay. #TwitJC -9:17 PM
MedEdHelen re adverse events - surely the parameters measured would pick up adverse events - or
do you mean proper errors? #TwitJC -9:17 PM
tobyhillman @chrisking01 interesting that the text records no sig diff in days ventilated/ LOS
though, but was diff in survivors. #twitjc -9:17 PM
twitjournalclub And lastly, Q10: How can the outcomes of this paper be applied? What's its
significance? What did the paper (fail to) consider? ^fd #twitjc -9:18 PM
peds_id_doc @MedEdHelen adverse events don't have to be errors...just bad luck #Twitjc -9:18 PM
TWSY RT @MedEdHelen: re adverse events - surely the parameters measured would pick up adverse
events - or do you mean proper errors? #twitjc -9:18 PM
silv24 @fidouglas more aggressive fluid resucitation, blood transfuions earlier, use of vasopressors
earlier....all could impact #twitjc -9:19 PM
peds_id_doc Dammit, my youngest just woke up....may have to cut and run... #Twitjc -9:19 PM
JoBrodie @twitjournalclub Did results have to be repeated or was this paper meant to be definitive
on the topic? Was guidance tweaked? #twitjc -9:19 PM
fidouglas @peds_id_doc Awww. Get them to join in! Never too young to start developing a social
media addiction. #twitjc -9:19 PM
MedEdHelen @tobyhillman @chrisking01 yes, I thought that the most interesting. Does that mean
we're bad at predicting regardless of treatment? #TwitJC -9:19 PM
northern_doctor Application of paper to other centres is most crucial point - main limitation of
study was that it was single centre only #twitjc -9:20 PM
simonpeteryoung #TwitJC there's a recent editorial with very good discussion points on this
paper - can anyone remember where it was? -9:20 PM
northern_doctor Not saying results/protocols aren't transferable, but that's not what study is set
up to show #twitjc -9:20 PM
amcunningham @silv24 @fidouglas but agree that adverse outcomes would be covered within
those assessed #TwitJC -9:20 PM
anaestheticdoc i think the outcomes can be easily implemented, Just a case of doing what we do,
but better and quicker, focusing on the goals. #twitjc -9:20 PM
themattmak #Twitjc @twitjournalclub easy! We're all using sepsis bundles and this led to the
Surviving Sepsis Campaign... -9:20 PM
tobyhillman @MedEdHelen or good at delaying the inevitable in some cases. Not possible to predict
beneficiaries prospectively though I guess. #twitjc -9:21 PM
chrisking01 @tobyhillman just read that now.. at the risk of sounding naive what does this mean in
clinical context though? #twitjc -9:21 PM
northern_doctor "Standard treatment" can vary between hospitals, but the fact we're all using
sepsis bundles speaks very clearly! #twitjc -9:21 PM
simonpeteryoung #TwitJC maybe PACMAN study would have been better targeting first few
hours -9:22 PM
TWSY @twitjournalclub Applicability issue 1 Rivers' patients sicker than the ones we would get in the
UK fitting this criteria, I'm told #twitjc -9:22 PM
themattmak #Twitjc my hospital is one of the participants of a new multi centre trial looking at
Protocolised Management in Sepsis -9:22 PM
TWSY @twitjournalclub Applicability issue 2 Our EDs not resourced to be able to do this... #twitjc -
9:23 PM
northern_doctor @amcunningham They may well be (and probably are) - just saying that only
studying single centre limits default wider application #twitjc -9:23 PM
MedEdHelen yes, massively influential in the literature "Cited by over 100 PubMed Central articles"
http://t.co/ndt1sFp #TwitJC -9:23 PM
JoBrodie @themattmak That's a good name, at least it includes the word 'sepsis' :) #twitjc -9:23 PM
tobyhillman @amcunningham logistics / skills to 'do' egdt in local DGH ? Prepared to be told I'm
wrong. #twitjc @northern_doctor -9:23 PM
AandE_SHO #twitjc sepsis bundle pathways are not correctly implemented in my experience and
usually referenced inappropriately -9:24 PM
silv24 The Surviving Sepsis Campaign - the impact of care bundles is clearly seen in everyday practice
#twitjc -9:24 PM
amcunningham @DoconaLimb there was 15% absolute reduction so ok:) #TwitJC -9:24 PM
JoBrodie Good point MT @northern_doctor: @amcunningham ...Just saying that only studying
single centre limits default wider application #twitjc -9:24 PM
anaestheticdoc @TWSY @twitjournalclub ED dont have to be implementing it, just need to get
patient to ITU quicker and start it there. #twitjc -9:24 PM
northern_doctor In real life we're all (or should be) identifying & treating septic patients earlier
than used to, and getting them to HDU #twitjc -9:24 PM
DrDLittle It is common sense that early, directed interventions will improve outcome. ?Same theory
applicable elsewhere #Twitjc -9:24 PM
peds_id_doc @TWSY @twitjournalclub I think resources are a key point - research is useless if
can't be applied. #Twitjc -9:24 PM
fidouglas Is this the first study of its kind? If so, isn't it logical that you would start small, then if it
works, try on a bigger scale? #twitjc -9:24 PM
TWSY @twitjournalclub Applicability issue 3 There was some talk about conflicts of interest and
Rivers... I don't know detail #twitjc -9:25 PM
tobyhillman @chrisking01 people take a long time to die in hospital but get out quickly if they get
better? #twitjc -9:25 PM
drgrumble @northern_doctor Getting them to HDU? That's a delay. It's treating them ASAP.
#TwitJC -9:25 PM
Derminatrix RT @northern_doctor: In real life we're all (or should be) identifying & treating septic
patients earlier than used to, and getting them to HDU #twitjc -9:25 PM
madlawstudent loving the #twitjc just about following you all! -9:26 PM
tobyhillman @northern_doctor if you have an hdu for 'medical' patients #twitjc -9:26 PM
northern_doctor @drgrumble Only after initial treatment started, obviously. I rarely see CVP lines
put in whilst in A&E. Fluids & abx, yes. #twitjc -9:26 PM
TWSY @anaestheticdoc @TWSY @twitjournalclub Get to ICU quicker if there is a bed on ICU #twitjc
-9:26 PM
simonpeteryoung #TwitJC applicability less clear with de novo cases of sepsis in-hospital;
presentation >24h to ICU; healthcare-acquired infections -9:27 PM
kevfrost @drgrumble Sepsis bundles initiated in A&E, with transfer to HDU if meets certain criteria
#twitjc -9:27 PM
JoBrodie Was the mortality rate for standard sepsis therapy at that study centre, and at that time,
much different from rate elsewhere? #twitjc -9:27 PM
silv24 Sadly sepsis is still not managed as well as it should be in - even with clinical guidelines #twitjc
-9:27 PM
tobyhillman @anaestheticdoc @TWSY @twitjournalclub really, a quick transfer to Itu from the
front door? Occupancy often 2 high 2 make practical #twitjc -9:28 PM
northern_doctor Interestingly, they don't mention training of A&E staff. IMHO that's as important
as the protocols themselves. #twitjc -9:28 PM
fidouglas @TWSY Unsourced(?!) on wiki: Rivers has not gained from any propriety research in this
area and has no conflict of interest. #twitjc -9:28 PM
GabrielScally #Twitjc It is an odd title, 'goal-directed therapy'. Who can argue in favor of therapy
without goals? But the effect looks very impressive. -9:28 PM
northern_doctor "@silv24: Sepsis is still not managed as well as it should be in - even with clinical
guidelines" <-- Agree; see my last tweet #twitjc -9:28 PM
aj0610 @northern_doctor V true, all well and good having protocols but if staff aren't trained in
appropriate implementation then useless #twitjc -9:28 PM
silv24 RT @northern_doctor: Interestingly, they dont mention training of A&E staff. IMHO thats as
important as the protocols themselves. #twitjc -9:29 PM
drgrumble The patients were treated in a nine-bed unit in the emergency department. Why are we
talking about transferring the patient? #TwitJC -9:29 PM
GabrielScally It would be interesting to know about wider adoption in sepsis, as well as spread of
the concept to other critical illness. #Twitjc -9:29 PM
DrDLittle RT @northern_doctor: Interestingly, they dont mention training of A&E staff. IMHO thats
as important as the protocols themselves. #Twitjc -9:29 PM
tobyhillman @anaestheticdoc they used an a line too, a limiting factor in many settings. But agree
ITU 'on sea' in ED is ideal for these pts. #twitjc -9:30 PM
anaestheticdoc hate to say this but one individual can implement this treatment. Its that simple.
CVP and blood gases. Call the anaesthetist!! #twitjc -9:30 PM
JoBrodie RT @silv24 RT @northern_doctor: Intrstngly they dont mention training of A&E staff.
IMHO thats as important as protocols themselves. #twitjc -9:30 PM
welsh_gas_doc RT @anaestheticdoc: hate to say this but one individual can implement this
treatment. Its that simple. CVP and blood gases. Call the anaesthetist!! #twitjc -9:31 PM
drgrumble @DrDLittle @northern_doctor This may be why it was a single centre trial. This level of
intervention in the ED could be challenging. #TwitJC -9:31 PM
DrDLittle @aj0610 @silv24 yes, but also initiation of treatment #Twitjc -9:31 PM
amcunningham @drgrumble they were transferred to icu after 6hrs #TwitJC -9:31 PM
silv24 Yes - many still don't "speak sepsis" RT @aj0610: @silv24 Is that bcoz of delay in
diagnosis/recognition? #twitjc -9:31 PM
simonpeteryoung #TwitJC sepsis VERY complicated. see PIRO for the bits we can influence, and
bits we can't -9:32 PM
tobyhillman @welsh_gas_doc @anaestheticdoc if needs the anaesthetist, whole system of care has
failed. Need multiple skilled peeps, not just one.#twitjc -9:32 PM
MedEdHelen They do mention the set up and the staff (treatment section of methods), and
reference a study from the same dept (3) #TwitJC -9:32 PM
northern_doctor Yes, an anaesthetist is the person you want with you on shop floor, but staff need
to know how to recognise those patients #twitjc -9:32 PM
kashfarooq @silv24 Love the #twitjc idea. May steal it for, say, #astrojc or #physicsjc Would we
have to pay royalties? ;-) -9:33 PM
silv24 @amcunningham not recognised early enough, not treated early enough...one of my major
bugbears #twitjc -9:33 PM
TWSY @fidouglas @TWSY Spoke from memory and can't source it. It may be untrue #twitjc -9:33
PM
welsh_gas_doc Even after this paper and the following Sepsis Bundles, some hospital labs still
won't even give you a lactate!! #TwitJC -9:33 PM
Derminatrix RT @drgrumble: This may be why it was a single centre trial. This level of intervention
in the ED could be challenging. #TwitJC -9:33 PM
silv24 Indeed - especially delay in giving antibiotics!! RT @DrDLittle: @aj0610 @silv24 yes, but also
initiation of treatment #Twitjc -9:33 PM
MedEdHelen I think that this is more about early goal directed therapy than it is about sepsis.
*discuss* #TwitJC -9:33 PM
iamdoctord Calling an anaesthetist isn't the only answer, we need all members of the team to
recognise the problem and initiate early therapy! #twitjc -9:33 PM
simonpeteryoung @anaestheticdoc it's an interesting argument. Try and train all to manage
(badly?), or a have a 'sepsis team' like the trauma team #twitjc -9:33 PM
chimenet “@DrDLittle: Shorter hospital stay = cheaper #Twitjc”< but under PbR means income
reduction for Trust? -9:33 PM
tobyhillman @northern_doctor or anyone who can put in a cvc and treat with fluids. #twitjc
medics/ surgeons should all be able to do similar -9:34 PM
anaestheticdoc Thats because anaesthetist is only ones who seem able to put CVP lines in these
days #twitjc -9:34 PM
AandE_SHO #twitjc we start abx as soon as a focus is ascertained, and if not, rule out any other
differentials and consider co-morbidities, sod medreg -9:34 PM
fidouglas @TWSY Like many things, it's highly unlikely that the info is available on the net. No
massive COI disclosed in the paper tho... #twitjc -9:34 PM
anaestheticdoc RT @simonpeteryoung: its an interesting argument. Try and train all to manage
(badly?), or a have a sepsis team like the trauma team #twitjc -9:34 PM
adriamarilla RT @silv24: Yes - many still don't "speak sepsis" RT @aj0610: @silv24 Is that bcoz of
delay in diagnosis/recognition? #twitjc -9:34 PM
rodedun Maybe we should incorporate #teddybearclub #geekdayout with and to celebrate success of
#twitjc tonight thoughts! -9:35 PM
iaintrk @silv24 apologies for missing journal club - will be there next week promise! #twitjc -9:35
PM
amcunningham @drgrumble but surely there is only point in intervention if ICU transfer possible?
#TwitJC -9:35 PM
TWSY Summary: important, valid up to a point and ... may be applicable depending? #twitjc -9:35
PM
Derminatrix Via @northern_doctor: Staff need to know how to recognise those patients #twitjc -
9:35 PM
northern_doctor @tobyhillman In theory. I've never done a CVC though, so wouldn't be happy to
go it alone. Support always available (so far!) #twitjc -9:35 PM
silv24 @welsh_gas_doc and so many forget to do a lactate check - drives me mad. I teach med
students about sepsis alot! #twitjc -9:35 PM
iamdoctord @anaestheticdoc we're expected to learn CVP line insertion for core medical training,
doing renal med was a bonus! #twitjc -9:36 PM
aj0610 @DrDLittle @AandE_SHO Surely take bloods etc for culture then start empirical abx?
#twitjc -9:36 PM
chimenet “@DrDLittle: I could do with learning some stats! #Twitjc”< Normal, Poisson, Standard
distributions. Bit of Chi squared & voila, expert.. -9:36 PM
welsh_gas_doc .@silv24 Good. Someone has too. Because recognition and management of sepsis
sure as hell isn't taught properly by UG Curriculum! #TwitJC -9:36 PM
Assidens RT @silv24: @amcunningham not recognised early enough, not treated early enough...one
of my major bugbears #twitjc -9:37 PM
Assidens RT @welsh_gas_doc: .@silv24 Good. Someone has too. Because recognition and
management of sepsis sure as hell isn't taught properly by UG Curriculum! #TwitJC -9:37 PM
DrGDH Just discovered #twitjc , bit late to the party, and a shame cause who doesn't love a bit of
EGDT? Twitter JC... Fantastic idea! -9:37 PM
simonpeteryoung #TwitJC I do think putting a CVC in is NOT the key. Piss poor interpretation of
clinical signs and measurements is what'll kill patients -9:37 PM
northern_doctor Summary: Well-executed study; significant results; supports early monitoring &
rx; good basis for current guidelines #twitjc -9:37 PM
TWSY @silv24 @fidouglas Well done. Great idea well executed. #twitjc -9:38 PM
JoBrodie What are the current guidelines for sepsis management, and do they reference this paper?
#twitjc -9:38 PM
silv24 RT @northern_doctor: Well-executed study; significant results; supports early monitoring &
rx; good basis for current guidelines #twitjc -9:38 PM
MedEdHelen @simonpeteryoung agreed..... and a bad system for getting care to patients when they
need it. #TwitJC -9:38 PM
iamdoctord Central line placement is a great skill, but needs the resources 'on-site' to be used
effectively, even in MAU/HDU setting... #twitjc -9:38 PM
JoBrodie This x100 :) RT @TWSY: @silv24 @fidouglas Well done. Great idea well executed. #twitjc -
9:38 PM
tobyhillman RT @simonpeteryoung: #TwitJC I do think putting a CVC in is NOT the key. Piss poor
interpretation of clinical signs and measurements is what'll kill patients -9:39 PM
fidouglas @DrGDH We'll put an abridged transcript up online, as well as a post summarising the
discussion. Follow @TwitJournalClub for updates #twitjc -9:39 PM
northern_doctor I'm signing off - thanks folks, it's been fun! #twitjc -9:39 PM
tobyhillman RT @TWSY: @silv24 @fidouglas Well done. Great idea well executed. #twitjc -9:39
PM
rodedun From the little that I know, I don't think that the importance of sepsis get's the recognition
it deserves in our teaching #twitjc -9:39 PM
welsh_gas_doc @silv24 and @fidouglas should be VERY proud with how well this has gone
tonight. Looking forward to more next week!! #TwitJC -9:39 PM
silv24 Thank you all so much for your contributions - I am over the moon #twitjc -9:39 PM
northern_doctor Vote of thanks to @fidouglas and @silv24 - massive success; you guys deserve a
lot of credit! #twitjc -9:40 PM
DrDLittle RT @welsh_gas_doc: @silv24 and @fidouglas should be VERY proud with how well this
has gone tonight. Looking forward to more #Twitjc -9:40 PM
twitjournalclub Thank you all very much for participating this evening. I've certainly had great fun!
^fd #twitjc -9:40 PM
kevfrost Ditto from me :) RT @northern_doctor: I'm signing off - thanks folks, it's been fun! #twitjc
-9:40 PM
Derminatrix Agreed! RT @TWSY: @silv24 @fidouglas Well done. Great idea well executed. #twitjc
-9:40 PM
twitjournalclub We'll put an abridged transcript and a summary blog post online in the next day or
so. ^fd #twitjc -9:40 PM
JoBrodie @silv24 @fidouglas Thank you for coming up with the idea and implementing it :) Really
enjoyed it. #twitjc -9:40 PM
aj0610 What a fab first chat tonight was - will be back next week! #twitjc -9:40 PM
DrDLittle Right, @frolickingfood is calling for attention, time to go. Well done all involved. #Twitjc -
9:40 PM
MedEdHelen Quite, Props to you both. RT @Derminatrix: Agreed! RT @TWSY: @silv24 @fidouglas
Well done. Great idea well executed. #TwitJC -9:40 PM
AandE_SHO @aj0610 @DrDLittle exactly, large bore/central access if need, gas, cultures! treat
empirically.. conservatively if needed #twitjc -9:41 PM
iamdoctord This has been great thank you! RT @twitjournalclub: Thank you all very much for
participating this evening. #twitjc -9:41 PM
twitjournalclub And of course, feel free to use the #TwitJC hashtag to continue discussing the
paper. #twitjc -9:41 PM
medicscott Well done all, especially @silv24 and @fidouglas. Great experience, I eagerly await next
Journal Club discussion #twitjc -9:41 PM
benazevedo @JoBrodie: Found this. RT: What are the current guidelines for sepsis management?
http://bit.ly/jbACzU #twitJC -9:41 PM
silv24 RT @DrDLittle: RT @welsh_gas_doc: @silv24 and @fidouglas should be VERY proud with
how well this has gone tonight. Looking forward to more #Twitjc -9:41 PM
AandE_SHO @aj0610 @DrDLittle cultures are rearely done appropriately by any walk of life #twitjc
-9:41 PM
silv24 Thank you all and thank you to my partner in crime @fidouglas - really enjoyed it and look
forward to next week #twitjc -9:42 PM
DrDLittle Really enjoyed the first #twitjc even if it was a topic I knew little about! A great success,
well done @fidouglas and @silv24 #Twitjc -9:42 PM
KP_LD @silv24 #twitjc looks very interesting! Let me know if you ever have a psychology related
paper :) -9:42 PM
chrisking01 RT @aj0610: @northern_doctor V true, all well and good having protocols but if staff
aren't trained in appropriate implementation then useless #twitjc -9:43 PM
simonpeteryoung #TwitJC this was AMAZING! well done all. I will be highlighting this to our
cabinet secretary for health (she's on twitter) -9:43 PM
twitjournalclub Next week, we'll be looking at Geoffrey Rose's 'Prevention Paradox' (BMJ, 1981).
#twitjc -9:43 PM
peds_id_doc HUGE CONGRATS to @fidouglas and @silv24 on the inaugural twitter journal club.
Amazing international achievement. #Twitjc -9:43 PM
doctorblogs .@silv24 @fidouglas another great EBM resource: critical appraisal tools etc
http://bit.ly/m56pcd from @cebmblog #twitjc -9:43 PM
parkerflash RT @welsh_gas_doc: @silv24 and @fidouglas should be VERY proud with how well
this has gone tonight. Looking forward to more next week!! #TwitJC -9:43 PM
amcunningham @drgrumble but surely this wasn't a trial of whether rx could be carried out in ED
alone? #TwitJC -9:43 PM
fidouglas @KP_LD I really like health psychology and psychiatry stuff. So I doubt it'll be too long
yet...! #twitjc -9:44 PM
silv24 RT @twitjournalclub: Next week, we'll be looking at Geoffrey Rose's 'Prevention Paradox'
(BMJ, 1981). #twitjc -9:44 PM
silv24 RT @peds_id_doc: HUGE CONGRATS to @fidouglas and @silv24 on the inaugural twitter
journal club. Amazing international achievement. #Twitjc -9:44 PM
chrisking01 RT @welsh_gas_doc: @silv24 and @fidouglas should be VERY proud with how well
this has gone tonight. Looking forward to more next week!! #TwitJC -9:44 PM
hullodave RT @twitjournalclub: Next week, we'll be looking at Geoffrey Rose's 'Prevention Paradox'
(BMJ, 1981). #twitjc -9:45 PM
fidouglas Thanks to everyone for saying 'well done', and to Natalie (@silv24) for helping pull
everything together! I *really* enjoyed that. #twitjc -9:45 PM
DrDLittle RT @twitjournalclub: Next week, well be looking at Geoffrey Roses Prevention Paradox
(BMJ, 1981). #Twitjc -9:46 PM
parkerflash RT @anaestheticdoc: @silv24 @fidouglas well done ladies congrats #twitjc -9:47 PM
AandE_SHO does #twitjc count as revising? -9:47 PM
anaestheticdoc got to get 2hours of CPD for that.Anyone a fancy a 9pm start. Kids need putting
bed normally #twitjc -9:47 PM
ashleighmartin1 Really enjoyed reading all your tweets in #twitjc sadly I didn't read the paper
thoroughly enough to contribute...maybe next week! -9:47 PM
simonpeteryoung #TwitJC I shall also contact @RCoANews re: CPD value of this -9:48 PM
feralvarezlo RT @doctorblogs: .@silv24 @fidouglas another great EBM resource: critical appraisal
tools etc http://bit.ly/m56pcd from @cebmblog #twitjc -9:48 PM
ross71521 @welsh_gas_doc I've had more contact hours about Comm skills than sepsis, but surely
that's b/c sepsis is easier to teach? #TwitJC -9:49 PM
peds_id_doc Did you guys see #twitjc? @westr @astupple right up your alley. -9:49 PM
amcunningham RT @simonpeteryoung: #TwitJC I shall also contact @RCoANews re: CPD value
of this -9:49 PM
EasternDoc @silv24 @fidouglas well done ladies, really good stuff. Sorry to lurk but I was doing
eportfolio. Will be more involved next week #twitJC -9:50 PM
tobyhillman RT @anaestheticdoc: got to get 2hours of CPD for that.Anyone a fancy a 9pm start.
Kids need putting bed normally #twitjc -9:50 PM
silv24 RT @simonpeteryoung: #TwitJC I shall also contact @RCoANews re: CPD value of this -9:51
PM
amcunningham To move from a critical care paper to prevention paradox shows great breadth to
be covered in #TwitJC -9:51 PM
silv24 RT @simonpeteryoung: #TwitJC this was AMAZING! well done all. I will be highlighting this
to our cabinet secretary for health (she's on twitter) -9:51 PM
McConways Haven't a notion what they're talking about (smart medics) but #twitjc is brilliant. Any
other 'clubs' on twitter? I want to be in one. -9:51 PM
rodedun really enjoyed #twitjc. for those interested there will be a #teddybearclub #geekdayout in
London 18th June Primrose Hill all invited :) -9:52 PM
anaestheticdoc @welsh_gas_doc will have to see my paper on why teaching communication skills
is a waste of time. #twitjc -9:52 PM
adriamarilla @silv24 and @fidouglas #twitjc great idea! can't wait for the next discussion! Well
done and thanks everyone for share your views :) -9:53 PM
MedEdHelen I can't wait till we integrate recording these into BMJ Portfolio, will be onto our
techies about how tomorrow. @twitjournalclub #TwitJC -9:54 PM
silv24 RT @ffolliet: THIS is what twitter is all about @silv24 @fidouglas set up an online medical
journal club. brilliant work, well done #twitjc -9:55 PM
twitjournalclub RT @rodedun: really enjoyed #twitjc. for those interested there will be a
#teddybearclub #geekdayout in London 18th June Primrose Hill all invited :) -9:55 PM
summerdaisy I will definitely be joining in #TwitJC once my exams are over in 3 weeks time! -9:55
PM
anaestheticdoc @rodedun whats #teddybearclub, sounds like euphemism for something else to
me. Primrose Hill or hampstead heath? #twitjc -9:56 PM
amcunningham @drgrumble sorry but this doesn't really tell us anything about transfer delay..
Well I don't see how it does #TwitJC -9:56 PM
chrisking01 “@ffolliet: THIS is what twitter is all about @silv24 @fidouglas set up an online
medical journal club. brilliant work, well done #twitjc -9:56 PM
amcunningham @drgrumble sorry I meant how transfer causes delay... #TwitJC -9:58 PM