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Journal Club 6/8/2020

Hello everyone! Welcome to the third session of Journal Club with tutor Dr Kirolos Michael.

The article for the week will be released at 17:55 on our Journal Club Facebook event. This gives you 20 minutes to analyse the paper mimicking the time given for AFP interviews. We will then begin promptly at 18:15 for our discussion which will take place on our online chatroom.

Link to Journal Club event page: https://www.facebook.com/events/286676695949971/

Link to the chat room: Journal Club Discussion

The discussion from the paper will be saved below this post if you need to refer back later. Enjoy!

Jacob Barnaby

Jacob Barnaby

6:15 pm
yep
Danish HaFeez

Danish HaFeez

6:15 pm
yes
Nosa Uwadiae
Won Young Yoon

Won Young Yoon

6:15 pm
Yes
Jacob Barnaby

Jacob Barnaby

6:16 pm
Beth Clayton, yep
Kirolos Michael

Kirolos Michael

6:16 pm
Hello everyone. Welcome back to anyone who's attended before. For anyone who is new, welcome. I'm Kirolos (CT1 Urology) and I will be your tutor
Cameron Lynch

Andy Jackson

6:16 pm
Anyone know how I can join this chat please?
Kirolos Michael

Kirolos Michael

6:16 pm
Thanks for all the feedback & for those who have been in contact via email. I go through it every week
Kirolos Michael

Kirolos Michael

6:17 pm
Just some housekeeping. As a journal club, the expectation is that everyone participates and shares ideas & is involved in the discussion. As the tutor, I am here to facilitate the discussion and provide a structure for the session. We will explore certain new topics/concepts, but we can’t go into too much detail (for the sake of keeping sessions to a reasonable time).
Kirolos Michael

Kirolos Michael

6:17 pm
So for anyone who's just joined us, the theme for this week was neurosurgery
Kirolos Michael

Kirolos Michael

6:18 pm
In the last few weeks, we've reviewed a few cohort studies. This week is a little different to try to mix things up a little & appreciate different types of articles
Kirolos Michael

Kirolos Michael

6:18 pm
Did everyone find the paper ok?

Andy Jackson

6:19 pm
Is there a paper ?
Annabel Chadwick

Annabel Chadwick

6:19 pm
Kirolos Michael

Kirolos Michael

6:19 pm
I'm not expecting anyone to fully understand the finer details

Andy Jackson

6:20 pm
Thankyou
Kirolos Michael

Kirolos Michael

6:20 pm
shall we get started
Callum Docherty
Kirolos Michael

Kirolos Michael

6:21 pm
can anyone summarise briefly the aim of this article?
Annabel Chadwick

Annabel Chadwick

6:22 pm
a systematic review to determine if the use of fluorescence guided surgery helps improve the extent of resection in low grade glioma
Jacob Barnaby

Jacob Barnaby

6:22 pm
To review the use of 5-AA in LGGs, gauging how effective it is in marking out the cancerous tissue
Danish HaFeez

Danish HaFeez

6:22 pm
to study the use of 5-aminolevulinic acid in low-grade glioma resection and evaluate positive fluroscence/effect on extent of resection
Divine Dominic

Divine Dominic

6:22 pm
Kirolos Michael, i don't think i particularly understand the basic details but will try get involved in the discussion as best i can😬
Kirolos Michael

Kirolos Michael

6:22 pm
fantastic all three of you
Kirolos Michael

Kirolos Michael

6:23 pm
Divine Dominic, that's not a problem, systematic reviews are new to many people
Tricia Tay
Kirolos Michael

Kirolos Michael

6:24 pm
so gliomas are tumours of the brain, often treated with excision. They can be low-grade or high-grade. Because gliomas are infiltrative, that means brain cells can be widely spread beyond the margin of the tumour that can be seen in surgery, there is interest in finding ways to "stain" the full extent of these tumours to make for a more complete resection, therefore improving pronosis
Kirolos Michael

Kirolos Michael

6:25 pm
In high-grade tumours, 5-ALA is a fluorescent dye that is used to improve the extent of resection
Kirolos Michael

Kirolos Michael

6:25 pm
what we don't know is if it would also improve the extent of resection in low-grade tumours (LGG)
Kirolos Michael

Kirolos Michael

6:25 pm
so that's a little background around the topic
Kirolos Michael

Kirolos Michael

6:25 pm
what kind of study is this? and why is it what it is?
Kirolos Michael

Kirolos Michael

6:26 pm
*infiltrative, that means tumour cells can be widely spread beyond the margin of the tumour (my bad)
Danish HaFeez

Danish HaFeez

6:27 pm
A systematic review- as a search criteria was used across 4 databases and all title/abstracts of the results were screened for inclusion making it systematic
Kirolos Michael

Kirolos Michael

6:27 pm
great description
Danish HaFeez

Danish HaFeez

6:28 pm
and the study was compliant with PRISMA systematic review guidelines
Kirolos Michael

Kirolos Michael

6:28 pm
so this is a systematic review
Kirolos Michael

Kirolos Michael

6:28 pm
everyone clear what a systematic review is?

Emma Mackender

6:28 pm
Not really (sorry)
Jacob Barnaby

Jacob Barnaby

6:28 pm
Systematic review - looking at a combination of prospective and retrospective studies. I think they've chosen this because they want to gauge the effectiveness of it's clinical use so it's best to review all the studies that have been already done on this, as it results in more high-powered evidence, vs doing your own study with a smaller n.
Kirolos Michael

Kirolos Michael

6:29 pm
That's right Jacob
Kirolos Michael

Kirolos Michael

6:31 pm
when we want to ask a clinical question, you can do what's called a systematic review. This involves setting a question like they have in this paper. Then you go through all articles that have been published in the past that help to answer this question. You put in place inclusion & exclusion criteria for choosing these papers to look at. So essenstially, you run a search on a database like pubmed with the key words you have chosen, then somebody sits and reads the titles, then abstracts, then the full body to see if they can include it or not into the systematic review based on the criteria you set
Kirolos Michael

Kirolos Michael

6:32 pm
the papers you are left with are analysed to help integrate the evidence from all the studies that are relevant
Divine Dominic

Divine Dominic

6:32 pm
what are some other types of reviews? i think ive only come across systematic reviews?
Kirolos Michael

Kirolos Michael

6:32 pm
this makes systematic reviews one of the highest levels of evidence of any articles (bar meta--analysis)

Akshara Sharma

6:32 pm
are all systematic reviews invited?

Hadis Reyhani

6:33 pm
in the selection criteria it says inclusion and exclusion criteria were defined a priori- what does this mean sorry?
Kirolos Michael

Kirolos Michael

6:34 pm
Divine Dominic, in clinical practice, systematic reviews are really the only main type of review relevant. Because they are systematic, you avoid the bias of picking and choosing papers you like. You can have non-systematic reviews but they are of limited use. They just detail for example advances in a particular field etc.
Danish HaFeez

Danish HaFeez

6:34 pm
Scoping reviews are another type of review- where the authors can pick which articles they want to include at their discretion rather than having to check all titles/abstracts against their inclusion/exclusion criteria
Kirolos Michael

Kirolos Michael

6:34 pm
Danish HaFeez, Absolutely. these reviews are helpful at discussing recent trends in a speciality for example
Kirolos Michael

Kirolos Michael

6:34 pm
Hadis Reyhani, Very good question
Kirolos Michael

Kirolos Michael

6:35 pm
for a systematic review to be effective/valid, the inclusion/exclusion criteria must be selected a priori
Kirolos Michael

Kirolos Michael

6:35 pm
that means "before" they run the search
Kirolos Michael

Kirolos Michael

6:36 pm
that way, they don't do a search first, see what papers are out there and then put in criteria they know will flag up papers they like or find interesting. This would lead to bias
Kirolos Michael

Kirolos Michael

6:36 pm
alright, let's move to the methods
Kirolos Michael

Kirolos Michael

6:36 pm
What was the population of interest?
Kirolos Michael

Kirolos Michael

6:36 pm
& what was the selection criteria?

Akshara Sharma

6:37 pm
if patients with LGG who had a surgical resection using 5ALA flouroscence

Gagana Mallawaarachchi

6:37 pm
Patients with LGG who had resection w 5-ALA
Divine Dominic

Divine Dominic

6:37 pm
patients with LGG who underwent FGS resection of the tumour using 5-ALA

Akshara Sharma

6:38 pm
patients who underwent biopsy were excluded
Kirolos Michael

Kirolos Michael

6:38 pm
Fantastic, nice and simple

Emma Mackender

6:38 pm
Patients with LGG who underwent surgical resection only, using 5-ALA.
Kirolos Michael

Kirolos Michael

6:38 pm
So just resections of low-grade gliomas with 5-ALA & no biopsies
Kirolos Michael

Kirolos Michael

6:38 pm
Have a look at page 3 guys
Kirolos Michael

Kirolos Michael

6:38 pm
this is what you should look for in a systematic review
Kirolos Michael

Kirolos Michael

6:39 pm
You have the flow-chart detailing the number of studies at each stage that made it & those that didn't
Kirolos Michael

Kirolos Michael

6:39 pm
and in Table 1, you have the names of all the studies that made the final cut (12), the number of patients, type of study etc.
Kirolos Michael

Kirolos Michael

6:40 pm
On to the results
Kirolos Michael

Kirolos Michael

6:40 pm
Can anyone briefly summarise the main findings of the systematic review? (I'm not expecting any level of detail)

Akshara Sharma

6:41 pm
overall, there is low correlation between 5 ALA and low grade glioma

Gagana Mallawaarachchi

6:41 pm
5-ALA wasn’t particularly helpful in the resection of LGL
Kirolos Michael

Kirolos Michael

6:41 pm
Everyone agree? Any other thoughts?
Danish HaFeez

Danish HaFeez

6:42 pm
Overall 5ALA was associated with low positive florescence rates in LGL- and the ones where it was better used more high tech/new optical visualization technologies
Kirolos Michael

Kirolos Michael

6:42 pm
All 3 of you are spot on
Annabel Chadwick

Annabel Chadwick

6:42 pm
there was a lot of heterogeneity between the included papers that limited how much they could be compared

Emma Mackender

6:42 pm
I think there may not be enough evidence to definitively say it's helpful/unhelpful ?
Divine Dominic

Divine Dominic

6:43 pm
i don't quite understand it but there a section that talks about the correlation between genetic profile of the glioma and the fluorescence?
Kirolos Michael

Kirolos Michael

6:43 pm
In summary, low-grade gliomas (LGG) had low positive fluorescence, so most of them didn't fluoresce
Kirolos Michael

Kirolos Michael

6:45 pm
Divine Dominic, yes, it does seem out of place doesn't it. I think they were trying to see if different low-grade tumours (which consist of different types of tumours with different genetic profiles) had different rates of uptakes. So for example, do all LGG have poor fluorescence or just some types?
Kirolos Michael

Kirolos Michael

6:45 pm
but I agree, it feels a little out of place in the middle
Kirolos Michael

Kirolos Michael

6:45 pm
Emma Mackender, could you elaborate a little more?
Kirolos Michael

Kirolos Michael

6:46 pm
(You've got a good point)

Emma Mackender

6:47 pm
Similar to what Annabel said & I'm unsure if the papers they have used actually fit their exact criteria
Kirolos Michael

Kirolos Michael

6:48 pm
Absolutely

Emma Mackender

6:48 pm
I'm assuming that's a difficulty when producing a SR
Kirolos Michael

Kirolos Michael

6:48 pm
Annabel Chadwick, that's a very good point. Could you explain what heterogeneity & why it's a downside?
Kirolos Michael

Kirolos Michael

6:49 pm
So the papers do fit their exact criteria, however the data from the papers is not heterogeneous
Annabel Chadwick

Annabel Chadwick

6:50 pm
It's the differences between the individual papers such as their populations and methodology (e.g. imaging used) if there's high heterogeneity it means there are numerous differences between the papers and it makes comparing them more difficult as you can't tell if the differences are due to the differences in the papers rather than actual differences in outcome
Danish HaFeez

Danish HaFeez

6:50 pm
might be jumping ahead a bit- but when looking at the strengths/weaknesses of a systematic review how do you distinguish from the strengths/weaknesses of how the SR was done and the strengths/weaknesses in the literature itself? Because the SR does pick up a lot of the current limitations/weaknesses in the literature regarding the use of 5ALA in LGG- but that itself is a strength of the SR. If that makes sense?
Kirolos Michael

Kirolos Michael

6:51 pm
Annabel Chadwick, that's right. So there is heterogeneity as you described in terms of different methodologies in each paper & different populations.
Kirolos Michael

Kirolos Michael

6:51 pm
The other type of heterogeneity is in terms of the data itself presented in each paper

Gagana Mallawaarachchi

6:52 pm
Kirolos, what did you mean by not heterogenous in the above message?

Gagana Mallawaarachchi

6:52 pm
I thought the data is heterogenous because of the variety of methods etc
Kirolos Michael

Kirolos Michael

6:53 pm
If all the papers had data presented in the same manner (for example an odds ratio or hazard ratio for the proportion of fluorescence of LGG), that would make the data homogenous & it means you can then extract equivalent data from each paper & satiatically analyse it with a forest plot & you'd get a meta-analysis which is the highest level of evidence in the literature
Kirolos Michael

Kirolos Michael

6:54 pm
Gagana Mallawaarachchi, does the above answer your question?
Kirolos Michael

Kirolos Michael

6:55 pm
So heterogenous because they have lots of different types of data in each article as well (in addition to the variety of methods)

Emma Mackender

6:55 pm
Ahh so there is high heterogeneity between the studies, so their data produced doesn't fit the criteria/ difficult to fulfil the aim?
Tricia Tay

Tricia Tay

6:55 pm
Does this then make it a weakness of the paper - ie it was not able to create a forest plot/meta-analysis of the heterogenous data available?

Gagana Mallawaarachchi

6:55 pm
Yes thank you
Kirolos Michael

Kirolos Michael

6:56 pm
Danish HaFeez, That's a very good point to pick up on. Today we will look at the strengths & weaknesses of the study design itself, not the strengths/weaknesses of the articles that they've looked at. We won't get into it, but in SRs, they will usually have a method of assessing the strength of the literature as part of their analysis
Kirolos Michael

Kirolos Michael

6:57 pm
Tricia Tay, that's certainly one way of looking at it. It's unfortunate that a meta-analysis couldn't be undertaken and a forest plot. That would be a weakness. However, this is only just because of the availability of the papers as well as the way the question was asked you could argue
Kirolos Michael

Kirolos Michael

6:58 pm
Any strengths?
Danish HaFeez

Danish HaFeez

6:58 pm
Kirolos Michael, Just to check- in this study they use the black criteria checklist to calculate a maximum quality index- is that what you mean by a method of assessing the strength of the literature? (sorry to go off track!)
Danish HaFeez

Danish HaFeez

6:59 pm
Kirolos Michael, strength would be that they summarise the literature well- identifying gaps in the literature that future research could address and provide practical recommendations on how that could be achieved
Kirolos Michael

Kirolos Michael

7:00 pm
Danish HaFeez, That's absolutely right. I can see you've read this article very thoroughly
Kirolos Michael

Kirolos Michael

7:01 pm
great with the strengths, anything else in terms of the methodology?
Annabel Chadwick

Annabel Chadwick

7:01 pm
they used the PRISMA checklist
Divine Dominic

Divine Dominic

7:02 pm
so what criteria has to be met for them to be able to do a forest plot? do the studies have to all have the same types of data
Annabel Chadwick

Annabel Chadwick

7:02 pm
two different authors performed the screening and a third author settled disagreements about whether a paper should be included or not

Hadis Reyhani

7:02 pm
the databases analysed were pubmed, google scholar and cochrane- key databases for important published work
Tricia Tay

Tricia Tay

7:02 pm
Strength - applied PRISMA checklist, large amount of studies identified spanning over a significant span of time (since inception to 2019)
Kirolos Michael

Kirolos Michael

7:03 pm
Annabel Chadwick, Fantastic points. PRISMA checklist for anyone who isn't familiar is a tool that can be used to construct a valid systematic review. It is literally a checklist of things to do
Kirolos Michael

Kirolos Michael

7:03 pm
Good points Hadis & Tricia
Jacob Barnaby

Jacob Barnaby

7:04 pm
Is the face that they checked the statistical reliability of the texts that the reviewers selected use Cohen's kappa a strength? (sorry this is poorly explained)
Jacob Barnaby

Jacob Barnaby

7:04 pm
*fact
Kirolos Michael

Kirolos Michael

7:05 pm
Divine Dominic, so in order to do a forest plot, you need the data from each paper to be presented in the same way. For example, they papers needed to have looked at the same measures and the numbers need to be presented in the same format (e.g. hazard ratio or odds ratio, with confidence intervals & p-values)
Kirolos Michael

Kirolos Michael

7:05 pm
only then can you undertake a forest plot
Kirolos Michael

Kirolos Michael

7:06 pm
Jacob Barnaby, yes so the fact they use some sort of statistical analysis is a strength (without getting into the stats here)
Divine Dominic

Divine Dominic

7:06 pm
okay thankyou, sorry i am new to this!
Kirolos Michael

Kirolos Michael

7:06 pm
Great strengths everyone, I'm quite impressed by how everyone has picked it up. These types of papers aren't easy to take in
Kirolos Michael

Kirolos Michael

7:06 pm
as a summary
Kirolos Michael

Kirolos Michael

7:06 pm
If asked about strengths of a systematic review, things to mention include: 1) Time frame (they looked at all papers ever published till 2019) (2) They used multiple databases (PUBMED, googlescholar, Cochrane etc.) (3) They looked at articles in all languages (not just English) (4) The inclusion & exlusion criteria was set a priori (before starting the search) (5) They had at least 2 people reviewing the articles independently & a third person as a tie breaker (6) The question was specific
Kirolos Michael

Kirolos Michael

7:07 pm
Any weaknesses?
Kirolos Michael

Kirolos Michael

7:07 pm
I'm happy to take any comments about the weaknesses of the methodology itself or just the nature of the question/articles therein
Danish HaFeez

Danish HaFeez

7:07 pm
They missed some big databases like medline/embasse?
Kirolos Michael

Kirolos Michael

7:08 pm
Good point, they could have included more databases
Kirolos Michael

Kirolos Michael

7:08 pm
We've already mentioned heterogeneity of articles
Kirolos Michael

Kirolos Michael

7:09 pm
just out of interest, does anyone know how they could reduced the heterogeneity?
Jacob Barnaby

Jacob Barnaby

7:09 pm
n = 12 is a fairly low number of papers?
Kirolos Michael

Kirolos Michael

7:09 pm
Bonus points

Hadis Reyhani

7:09 pm
all the studies they included were case series (low strength evidence)
Annabel Chadwick

Annabel Chadwick

7:09 pm
stricter inclusion criteria?
Kirolos Michael

Kirolos Michael

7:09 pm
Great point Jacob, some SRs will have hundreds of papers

Emma Mackender

7:09 pm
Kirolos Michael, have a narrower inclusion criteria?
Kirolos Michael

Kirolos Michael

7:10 pm
Annabel Chadwick, Spot on.
Tricia Tay

Tricia Tay

7:10 pm
To reduce heterogeneity - Could they have been more selective in their methods - ie include studies from certain timeframe or used a specific visualisation technique?
Danish HaFeez

Danish HaFeez

7:10 pm
would stricter inclusion criteria mean focusing on either retrospective/prospective studies?
Jacob Barnaby

Jacob Barnaby

7:11 pm
Could they write to the original authors and request the raw data from the studies - some of which may have some of the needed outcomes measures? Or is this too labour-intensive for an SR?
Kirolos Michael

Kirolos Michael

7:11 pm
That's right Emma & Annabel. You just make your inclusion criteria stricter. So for example, you only include studies that used a particular microscope and exclude every other type of microscope etc
Kirolos Michael

Kirolos Michael

7:11 pm
Jacob Barnaby, in theory they can, but it's too labour intensive. And that data will not have gone through peer-review so it doesn't tend to happen

Emma Mackender

7:12 pm
For a SR which studies would be preferred to be included, retrospective or prospective?
Kirolos Michael

Kirolos Michael

7:12 pm
Bear in mind an SR is a review, it should present anything new etc.
Kirolos Michael

Kirolos Michael

7:12 pm
Emma Mackender, it doesn't matter. Anything that fits the critera really. That is all
Kirolos Michael

Kirolos Michael

7:12 pm
in fact, this particular SR had a randomised-control-trial (RCT) included
Kirolos Michael

Kirolos Michael

7:14 pm
So to summarise, the main weaknesses are heterogeneity, possibly due to a broad inclusion criteria, few studies that met these criteria & inability to undertake a forest plot/meta-analysis to draw out any meaningful conclusion that could be statistically analysed to answer the question
Kirolos Michael

Kirolos Michael

7:14 pm
so in summary, has this study answered the question it set out to answer?
Kirolos Michael

Kirolos Michael

7:15 pm
Any final thoughts?
Jacob Barnaby

Jacob Barnaby

7:15 pm
It doesn't give a solid answer
Jacob Barnaby

Jacob Barnaby

7:16 pm
they allude to the idea that they need more evidence/"future studies" to give a better answer
Kirolos Michael

Kirolos Michael

7:16 pm
Agreed
Jacob Barnaby

Jacob Barnaby

7:16 pm
But they are semi-optimistic about the future of the technique
Danish HaFeez

Danish HaFeez

7:16 pm
partially- current data is limited and suggest 5-ALA is not currently that useful for resecting low-grade tumors but lays out future avenues of research which may help confirm/deny this
Kirolos Michael

Kirolos Michael

7:17 pm
Essentially, we've learnt that LGG don't fluoresce with 5-ALA as well as HGG do, but they are hopeful that refining the visualisation techniques with different microscopes and other imaging modalities could lead to promising results
Kirolos Michael

Kirolos Michael

7:18 pm
Danish HaFeez, spot on
Kirolos Michael

Kirolos Michael

7:18 pm
Any other comments?
Kirolos Michael

Kirolos Michael

7:18 pm
While we're wrapping up, I'd be very grateful if you could could complete this feedback form: https://forms.gle/b3VK8CdbMVMcHX1H9
Kirolos Michael

Kirolos Michael

7:19 pm
I know this article was a little more challenging compared to the last few weeks, but hopefully it's given you guys a flavour of systeamtic reviews and would be able to discuss the basic methodologies, strenghts & weaknesses
Kirolos Michael

Kirolos Michael

7:19 pm
as always, you can email me at kirolosmichael@gmail.com for any questions or suggestions
Tricia Tay

Tricia Tay

7:20 pm
Thank you for this session!
Annabel Chadwick

Annabel Chadwick

7:20 pm
thank you!

Emma Mackender

7:20 pm
Thank you, very helpful

Akshara Sharma

7:21 pm
Thank you.
Divine Dominic

Divine Dominic

7:21 pm
thankyou
Kirolos Michael

Kirolos Michael

7:21 pm
I'm very impressed by the discussion today
Jacob Barnaby

Jacob Barnaby

7:21 pm
Thank you for your time this evening

Hadis Reyhani

7:21 pm
thank you!
Kirolos Michael

Kirolos Michael

7:21 pm
You guys have demonstrated great critical thinking skills that can be applied in many different ways
Kirolos Michael

Kirolos Michael

7:21 pm
I know a few aren't too fond of the current chat function & have asked if if can be hosted on a different software. I've passed it onto scalpel and we'll look into different ways of improving it. Every software presents it's own challenges and there is no perfect solution
Won Young Yoon

Won Young Yoon

Reply
Thank you!