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Journal Club 27/3/2019
Quote from Deleted user on 25th April 2019, 5:45 pmDiscussion Edit
Journal Club
2
Daniel Lewis
Mar 27
Hi all
EdwinKoubeh
Mar 27
Hello
xenia sara
Mar 27
Hello everyone, welcome to this week’s journal club where we will be discussing “The use of atorvastatin for chronic subdural haematoma: a retrospective cohort comparison study”
Saad Salman
Mar 27
Hello Dr Lewis
Daniel Lewis
Mar 27
Thank you for joining, should we give people a few more minutes to join?
xenia sara
Mar 27
That’s a good idea, we can start formally in 5 minutes
Yanish Ramphul
Mar 27
Hello everyone
suhaibamin
Mar 27
Hi everyone!
xenia sara
Mar 27
Ok would it be alight to begin the conversation Dan?
xenia sara
Mar 27
*alright
Daniel Lewis
Mar 27
Sure thing, what did people think of the paper?
wkoubeh1
Mar 27
I think the paper provided a good starting point regarding the use of statins but doesn’t give a conclusive answer
EdwinKoubeh
Mar 27
I thought the paper was generally quite good but there were some issues with the method
Saad Salman
Mar 27
In conclusion i thought this was a decent paper, this comparison study Showed that it had a lower rate of deterioration
Daniel Lewis
Mar 27
Good points, was the clinical question a valid one?
suhaibamin
Mar 27
Very interesting to see how atorvastatin can be used for other purposes. I always thought it was exclusively used to treat high cholesterol
Saad Salman
Mar 27
What is the use of astrovastin for chronic subdural hematoma?
Saad Salman
Mar 27
i think it was more of reults and what they aim to find out
EdwinKoubeh
Mar 27
I think it could have been more specific and it should be phrased as a question rather than a statement
Daniel Lewis
Mar 27
So there questio was whwth
Daniel Lewis
Mar 27
was whether a statin could be used in patients with CSDH who do not undergo surgery
Daniel Lewis
Mar 27
as they acknowledge in the discussion though, this is only around 20% of patients, the rest have surgery at time of presentation
wkoubeh1
Mar 27
Yes, a substantial number of the CSDH patients were already on statins, so could not be included in the analysis
EdwinKoubeh
Mar 27
Yes, a lot already took statins for preexisting cardiovacular disorders but these were excluded
Daniel Lewis
Mar 27
Good point and it raises a major issue I have with this paper. Was this actually a retrospective cohort study?
Saad Salman
Mar 27
Yes it was
wkoubeh1
Mar 27
Yes. This potentially introduces more sources of bias I think
suhaibamin
Mar 27
True, but the Atorvastatin group showed significant improvement in treating CSDH compared to the control group after 3 months
Saad Salman
Mar 27
Making it less reliable
suhaibamin
Mar 27
I agree
Daniel Lewis
Mar 27
So in the study they weren’t recruiting people who were already on a statin, they were newly starting patients on the drug making this a clinical trial.
Daniel Lewis
Mar 27
And this for me raises a number of issues
Daniel Lewis
Mar 27
Did they have ethics to do this?
EdwinKoubeh
Mar 27
I am unsure if they got informed consent from the patients.
EdwinKoubeh
Mar 27
Also, a retrospective study should investigate the patients AFTER they have developed the outcomes of interest so I don’t think this study was actually a retrospective study
Yanish Ramphul
Mar 27
As far as i’m aware any research project like this one has to be run through an ethics committee first
suhaibamin
Mar 27
True, but in terms of beneficence, the doctor will have had more of an insight to make the right decision that most benefits the patients.
suhaibamin
Mar 27
But I agree, the ethical issues should have been evaluated before the study was carried out
Saad Salman
Mar 27
I think they would have asked for consent because it is important to ask for the patients permission before carrying out the procedure
Daniel Lewis
Mar 27
True, but the evidence base for statins as a treatment is very weak so I presume they had ethical approval for this study but it is not specified in the paper
suhaibamin
Mar 27
True, I think they should have referred to the ethical frameworks within the discussion
Daniel Lewis
Mar 27
Or in the methods, another issue not addressed is that if you look at Table 2 a number of patients had dementia. Did these patients have capacity to consent to participation in the study?
wkoubeh1
Mar 27
Most likely not but the doctors could have asked family
Saad Salman
Mar 27
I think it depends on how bad their dementia was, if the patients could consent they would have done. If not doctors would ask for family permission before carrying out the procedure
Daniel Lewis
Mar 27
Correct and indeed this is what they did in the previous statin study referenced in the paper.
suhaibamin
Mar 27
I assume they would have asked family members or a legal guardian if the patient was incapable to make a decision and give consent themselves
EdwinKoubeh
Mar 27
Whilst it may not be good in terms of autonomy, I think that they should not let a person with dementia decide themself
Daniel Lewis
Mar 27
In effect then, this was a non-randomised unblinded drug trial. How did they decide on what dose of statin to give people?
Saad Salman
Mar 27
Different groups were given different doses which produced a variety of results that could lead to their conclusion
EdwinKoubeh
Mar 27
They did use low doses in general which is a strength as it minimised side effects
suhaibamin
Mar 27
There was no dose-ranging study for Atorvastatin to be used for inflammation in patients, only clinical studies and several animal studies.
suhaibamin
Mar 27
There has only been a large dose-ranging study for Atorvastatin to treat cholesterol
Daniel Lewis
Mar 27
Precisely, so this paper and the previous paper they reference have maybe jumped the gun slightly. Normally when setting up a drug study you do phase 0 and phase 1 studies to establish if the drug reaches the intended site in the body and the optimum dose before testing clinical efficacy
suhaibamin
Mar 27
If I remember correctly they used a low dose of Atorvastatin.
EdwinKoubeh
Mar 27
They used the same doses as an ongoing study. That ongoing study may have shown that this specific does is optimal
Daniel Lewis
Mar 27
That is true they are using the same dose as an ongoing ranodmized controlled trial but a problem with this paper is that there is no real evidence presented that atorvastatin actually reaches the subdural space other than a rat study
wkoubeh1
Mar 27
So, we can’t be sure that the results of the study are as a result of the artorvastatin?
wkoubeh1
Mar 27
So, we can’t be sure that the results of the study are as a result of the artorvastatin?
wkoubeh1
Mar 27
So, we can’t be sure that the results of the study are as a result of the artorvastatin?
Saad Salman
Mar 27
we can but its not accurate
EdwinKoubeh
Mar 27
What about the previously reported preliminary study on CSDH patients. Would this not have shown that atorvastatin reaches the subdural space?
Daniel Lewis
Mar 27
Nope, in essence they have used the same low dose as in this paper with no real evidence that this is the best dose to use
Daniel Lewis
Mar 27
It may be that they are drastically underdosing patients and thereby diluting the treatment effect of the drug
Saad Salman
Mar 27
but if they used more dose would it not lead to any major side effects?
EdwinKoubeh
Mar 27
Ok
suhaibamin
Mar 27
There wouldn’t be a way to know without trying it right?
Saad Salman
Mar 27
in essence though suhaib it should
Daniel Lewis
Mar 27
It may do but without proper phase I studies we do not know if the unspecified dose they used is in any way effective at lowering inflammation space
Daniel Lewis
Mar 27
What do we think of their results?
EdwinKoubeh
Mar 27
I dont think their results were representative of the whole population as the average participant in the study was quite old
Saad Salman
Mar 27
I think that this comparison study has shown that CSDH with Atorvastatin had a lower rate of deterioration and burr-hole drainage. This initial promising result prompts further large-scale randomised controlled trial.
suhaibamin
Mar 27
Theoretically Saad it should yes. But as Dan just said without proper phase studies we wouldn’t know if a change in the dose actually effects the efficacy of lowering inflammation space
Saad Salman
Mar 27
Ok
suhaibamin
Mar 27
I feel like more research into the effects of Atorvastatin to treat imflammatory properties should have been carried out first before this trail was carried out
Saad Salman
Mar 27
yeah the results aren’t that accurate you need to look more into the dose of the atorvastin to treat the inflammatory propertieds
Daniel Lewis
Mar 27
Correct, I do feel like they have jumped into this clinical study without a proper evidence base. Did they find a difference in terms of their primary outcome – namely patient improvement at 3 months?
EdwinKoubeh
Mar 27
9 out of 12 improved after 3 months
EdwinKoubeh
Mar 27
but 5 out of 12 in the control group also improved
EdwinKoubeh
Mar 27
The difference isn’t that significant considering that the sample size is so small
suhaibamin
Mar 27
I agree
Saad Salman
Mar 27
I agree
Daniel Lewis
Mar 27
Was the result significant?
EdwinKoubeh
Mar 27
I think it is also important to consider that only 2 conditions worsened in the atorvastatin group but 7 worsened requiring burr-hole surgery in the control which is quite signifcant
EdwinKoubeh
Mar 27
I don’t think that the results are signifcant until more follow up study can evidence that the resulsts are reproducible
EdwinKoubeh
Mar 27
*studies
Daniel Lewis
Mar 27
Is everyone happy with the concept of statistical significance and p values?
suhaibamin
Mar 27
I don’t think it was significant. They should have used a larger sample size. But also done more research prior to this.
Saad Salman
Mar 27
what are p values Dr Lewis?
EdwinKoubeh
Mar 27
Effecyively how likely an observation is if it is left to chance
Daniel Lewis
Mar 27
Exactly Edwin its the probability that a result could occur by chance
Daniel Lewis
Mar 27
By convention we accept p values less than 0.05 as statistically significant.
Saad Salman
Mar 27
oh okay thanks yep i get it now
Daniel Lewis
Mar 27
Whilst there was higher improvement in the tstain group, the result was not statistically significant (P=0.0977)
Daniel Lewis
Mar 27
statin*
xenia sara
Mar 27
Just to let you all now journal club will be coming to a close in 5 minutes. Please prepare your leaving comments
wkoubeh1
Mar 27
I think the paper outlines an interesting prospect, but the study is not robust enough to arrive at a concrete judgement
suhaibamin
Mar 27
I believe that although the journal has a good purpose, more research should have been done into the efficacy of Atorvastatin at treating inflammation related cases, and which areas it is able to effectively reach. Then the study should be carried out again if there is still a low risk, but next time with a larger sample size and more ethical frameworks. But all in all, very interesting.
EdwinKoubeh
Mar 27
I think that there were quite a few issues with the method- namely the dosing, and the fact that the results aren’t representative. Also, the results are not statistically significant so whilst the study had some strengths such as the use of a control group, there were too many issues meaning that the findings shouldn’t be used in a clinical environment unless other studies find the same results.
Saad Salman
Mar 27
i think that the paper was quite interesting, was challenging to understand but with reading around it i was able to somewhat understand the study, however the results don’t give an accurate representation so could do with some more research for the best dose of the statin to treat this neurological condition. especially with an ageing population this would do benefit to society
xenia sara
Mar 27
Thank you all for attending this week’s journal club. I’ll let you know when the next one is happening and thank you so much to Dan for hosting Journal club once again!
wkoubeh1
Mar 27
thanks dan
suhaibamin
Mar 27
Thanks Dan, it was a pleasure. See everyone next time!
EdwinKoubeh
Mar 27
Thank you Dan
Saad Salman
Mar 27
thanks dr Lewis see u next week
Daniel Lewis
Mar 27
Hi all, sorry I had some home internet issues. Than you for attending the journal club and hopefully see you all the next one
Discussion Edit
Journal Club
2
Daniel Lewis
Mar 27
Hi all
EdwinKoubeh
Mar 27
Hello
xenia sara
Mar 27
Hello everyone, welcome to this week’s journal club where we will be discussing “The use of atorvastatin for chronic subdural haematoma: a retrospective cohort comparison study”
Saad Salman
Mar 27
Hello Dr Lewis
Daniel Lewis
Mar 27
Thank you for joining, should we give people a few more minutes to join?
xenia sara
Mar 27
That’s a good idea, we can start formally in 5 minutes
Yanish Ramphul
Mar 27
Hello everyone
suhaibamin
Mar 27
Hi everyone!
xenia sara
Mar 27
Ok would it be alight to begin the conversation Dan?
xenia sara
Mar 27
*alright
Daniel Lewis
Mar 27
Sure thing, what did people think of the paper?
wkoubeh1
Mar 27
I think the paper provided a good starting point regarding the use of statins but doesn’t give a conclusive answer
EdwinKoubeh
Mar 27
I thought the paper was generally quite good but there were some issues with the method
Saad Salman
Mar 27
In conclusion i thought this was a decent paper, this comparison study Showed that it had a lower rate of deterioration
Daniel Lewis
Mar 27
Good points, was the clinical question a valid one?
suhaibamin
Mar 27
Very interesting to see how atorvastatin can be used for other purposes. I always thought it was exclusively used to treat high cholesterol
Saad Salman
Mar 27
What is the use of astrovastin for chronic subdural hematoma?
Saad Salman
Mar 27
i think it was more of reults and what they aim to find out
EdwinKoubeh
Mar 27
I think it could have been more specific and it should be phrased as a question rather than a statement
Daniel Lewis
Mar 27
So there questio was whwth
Daniel Lewis
Mar 27
was whether a statin could be used in patients with CSDH who do not undergo surgery
Daniel Lewis
Mar 27
as they acknowledge in the discussion though, this is only around 20% of patients, the rest have surgery at time of presentation
wkoubeh1
Mar 27
Yes, a substantial number of the CSDH patients were already on statins, so could not be included in the analysis
EdwinKoubeh
Mar 27
Yes, a lot already took statins for preexisting cardiovacular disorders but these were excluded
Daniel Lewis
Mar 27
Good point and it raises a major issue I have with this paper. Was this actually a retrospective cohort study?
Saad Salman
Mar 27
Yes it was
wkoubeh1
Mar 27
Yes. This potentially introduces more sources of bias I think
suhaibamin
Mar 27
True, but the Atorvastatin group showed significant improvement in treating CSDH compared to the control group after 3 months
Saad Salman
Mar 27
Making it less reliable
suhaibamin
Mar 27
I agree
Daniel Lewis
Mar 27
So in the study they weren’t recruiting people who were already on a statin, they were newly starting patients on the drug making this a clinical trial.
Daniel Lewis
Mar 27
And this for me raises a number of issues
Daniel Lewis
Mar 27
Did they have ethics to do this?
EdwinKoubeh
Mar 27
I am unsure if they got informed consent from the patients.
EdwinKoubeh
Mar 27
Also, a retrospective study should investigate the patients AFTER they have developed the outcomes of interest so I don’t think this study was actually a retrospective study
Yanish Ramphul
Mar 27
As far as i’m aware any research project like this one has to be run through an ethics committee first
suhaibamin
Mar 27
True, but in terms of beneficence, the doctor will have had more of an insight to make the right decision that most benefits the patients.
suhaibamin
Mar 27
But I agree, the ethical issues should have been evaluated before the study was carried out
Saad Salman
Mar 27
I think they would have asked for consent because it is important to ask for the patients permission before carrying out the procedure
Daniel Lewis
Mar 27
True, but the evidence base for statins as a treatment is very weak so I presume they had ethical approval for this study but it is not specified in the paper
suhaibamin
Mar 27
True, I think they should have referred to the ethical frameworks within the discussion
Daniel Lewis
Mar 27
Or in the methods, another issue not addressed is that if you look at Table 2 a number of patients had dementia. Did these patients have capacity to consent to participation in the study?
wkoubeh1
Mar 27
Most likely not but the doctors could have asked family
Saad Salman
Mar 27
I think it depends on how bad their dementia was, if the patients could consent they would have done. If not doctors would ask for family permission before carrying out the procedure
Daniel Lewis
Mar 27
Correct and indeed this is what they did in the previous statin study referenced in the paper.
suhaibamin
Mar 27
I assume they would have asked family members or a legal guardian if the patient was incapable to make a decision and give consent themselves
EdwinKoubeh
Mar 27
Whilst it may not be good in terms of autonomy, I think that they should not let a person with dementia decide themself
Daniel Lewis
Mar 27
In effect then, this was a non-randomised unblinded drug trial. How did they decide on what dose of statin to give people?
Saad Salman
Mar 27
Different groups were given different doses which produced a variety of results that could lead to their conclusion
EdwinKoubeh
Mar 27
They did use low doses in general which is a strength as it minimised side effects
suhaibamin
Mar 27
There was no dose-ranging study for Atorvastatin to be used for inflammation in patients, only clinical studies and several animal studies.
suhaibamin
Mar 27
There has only been a large dose-ranging study for Atorvastatin to treat cholesterol
Daniel Lewis
Mar 27
Precisely, so this paper and the previous paper they reference have maybe jumped the gun slightly. Normally when setting up a drug study you do phase 0 and phase 1 studies to establish if the drug reaches the intended site in the body and the optimum dose before testing clinical efficacy
suhaibamin
Mar 27
If I remember correctly they used a low dose of Atorvastatin.
EdwinKoubeh
Mar 27
They used the same doses as an ongoing study. That ongoing study may have shown that this specific does is optimal
Daniel Lewis
Mar 27
That is true they are using the same dose as an ongoing ranodmized controlled trial but a problem with this paper is that there is no real evidence presented that atorvastatin actually reaches the subdural space other than a rat study
wkoubeh1
Mar 27
So, we can’t be sure that the results of the study are as a result of the artorvastatin?
wkoubeh1
Mar 27
So, we can’t be sure that the results of the study are as a result of the artorvastatin?
wkoubeh1
Mar 27
So, we can’t be sure that the results of the study are as a result of the artorvastatin?
Saad Salman
Mar 27
we can but its not accurate
EdwinKoubeh
Mar 27
What about the previously reported preliminary study on CSDH patients. Would this not have shown that atorvastatin reaches the subdural space?
Daniel Lewis
Mar 27
Nope, in essence they have used the same low dose as in this paper with no real evidence that this is the best dose to use
Daniel Lewis
Mar 27
It may be that they are drastically underdosing patients and thereby diluting the treatment effect of the drug
Saad Salman
Mar 27
but if they used more dose would it not lead to any major side effects?
EdwinKoubeh
Mar 27
Ok
suhaibamin
Mar 27
There wouldn’t be a way to know without trying it right?
Saad Salman
Mar 27
in essence though suhaib it should
Daniel Lewis
Mar 27
It may do but without proper phase I studies we do not know if the unspecified dose they used is in any way effective at lowering inflammation space
Daniel Lewis
Mar 27
What do we think of their results?
EdwinKoubeh
Mar 27
I dont think their results were representative of the whole population as the average participant in the study was quite old
Saad Salman
Mar 27
I think that this comparison study has shown that CSDH with Atorvastatin had a lower rate of deterioration and burr-hole drainage. This initial promising result prompts further large-scale randomised controlled trial.
suhaibamin
Mar 27
Theoretically Saad it should yes. But as Dan just said without proper phase studies we wouldn’t know if a change in the dose actually effects the efficacy of lowering inflammation space
Saad Salman
Mar 27
Ok
suhaibamin
Mar 27
I feel like more research into the effects of Atorvastatin to treat imflammatory properties should have been carried out first before this trail was carried out
Saad Salman
Mar 27
yeah the results aren’t that accurate you need to look more into the dose of the atorvastin to treat the inflammatory propertieds
Daniel Lewis
Mar 27
Correct, I do feel like they have jumped into this clinical study without a proper evidence base. Did they find a difference in terms of their primary outcome – namely patient improvement at 3 months?
EdwinKoubeh
Mar 27
9 out of 12 improved after 3 months
EdwinKoubeh
Mar 27
but 5 out of 12 in the control group also improved
EdwinKoubeh
Mar 27
The difference isn’t that significant considering that the sample size is so small
suhaibamin
Mar 27
I agree
Saad Salman
Mar 27
I agree
Daniel Lewis
Mar 27
Was the result significant?
EdwinKoubeh
Mar 27
I think it is also important to consider that only 2 conditions worsened in the atorvastatin group but 7 worsened requiring burr-hole surgery in the control which is quite signifcant
EdwinKoubeh
Mar 27
I don’t think that the results are signifcant until more follow up study can evidence that the resulsts are reproducible
EdwinKoubeh
Mar 27
*studies
Daniel Lewis
Mar 27
Is everyone happy with the concept of statistical significance and p values?
suhaibamin
Mar 27
I don’t think it was significant. They should have used a larger sample size. But also done more research prior to this.
Saad Salman
Mar 27
what are p values Dr Lewis?
EdwinKoubeh
Mar 27
Effecyively how likely an observation is if it is left to chance
Daniel Lewis
Mar 27
Exactly Edwin its the probability that a result could occur by chance
Daniel Lewis
Mar 27
By convention we accept p values less than 0.05 as statistically significant.
Saad Salman
Mar 27
oh okay thanks yep i get it now
Daniel Lewis
Mar 27
Whilst there was higher improvement in the tstain group, the result was not statistically significant (P=0.0977)
Daniel Lewis
Mar 27
statin*
xenia sara
Mar 27
Just to let you all now journal club will be coming to a close in 5 minutes. Please prepare your leaving comments
wkoubeh1
Mar 27
I think the paper outlines an interesting prospect, but the study is not robust enough to arrive at a concrete judgement
suhaibamin
Mar 27
I believe that although the journal has a good purpose, more research should have been done into the efficacy of Atorvastatin at treating inflammation related cases, and which areas it is able to effectively reach. Then the study should be carried out again if there is still a low risk, but next time with a larger sample size and more ethical frameworks. But all in all, very interesting.
EdwinKoubeh
Mar 27
I think that there were quite a few issues with the method- namely the dosing, and the fact that the results aren’t representative. Also, the results are not statistically significant so whilst the study had some strengths such as the use of a control group, there were too many issues meaning that the findings shouldn’t be used in a clinical environment unless other studies find the same results.
Saad Salman
Mar 27
i think that the paper was quite interesting, was challenging to understand but with reading around it i was able to somewhat understand the study, however the results don’t give an accurate representation so could do with some more research for the best dose of the statin to treat this neurological condition. especially with an ageing population this would do benefit to society
xenia sara
Mar 27
Thank you all for attending this week’s journal club. I’ll let you know when the next one is happening and thank you so much to Dan for hosting Journal club once again!
wkoubeh1
Mar 27
thanks dan
suhaibamin
Mar 27
Thanks Dan, it was a pleasure. See everyone next time!
EdwinKoubeh
Mar 27
Thank you Dan
Saad Salman
Mar 27
thanks dr Lewis see u next week
Daniel Lewis
Mar 27
Hi all, sorry I had some home internet issues. Than you for attending the journal club and hopefully see you all the next one