Quote from Scalpel on 6th August 2020, 7:27 pm

		Jacob Barnaby 6:15 pm yep
		Danish HaFeez 6:15 pm yes
		Won Young Yoon 6:15 pm Yes
		Jacob Barnaby 6:16 pm Beth Clayton, yep
		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
		Andy Jackson 6:16 pm Anyone know how I can join this chat please?
		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 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 6:17 pm So for anyone who’s just joined us, the theme for this week was neurosurgery
		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 6:18 pm Did everyone find the paper ok?
		Andy Jackson 6:19 pm Is there a paper ?
		Annabel Chadwick 6:19 pm @Andy https://academic.oup.com/ons/article/19/1/1/5673646?…
		Kirolos Michael 6:19 pm I’m not expecting anyone to fully understand the finer details
		Andy Jackson 6:20 pm Thankyou
		Kirolos Michael 6:20 pm shall we get started
		Kirolos Michael 6:21 pm can anyone summarise briefly the aim of this article?
		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 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 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 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 6:22 pm fantastic all three of you
		Kirolos Michael 6:23 pm Divine Dominic, that’s not a problem, systematic reviews are new to many people
		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 6:25 pm In high-grade tumours, 5-ALA is a fluorescent dye that is used to improve the extent of resection
		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 6:25 pm so that’s a little background around the topic
		Kirolos Michael 6:25 pm what kind of study is this? and why is it what it is?
		Kirolos Michael 6:26 pm *infiltrative, that means tumour cells can be widely spread beyond the margin of the tumour (my bad)
		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 6:27 pm great description
		Danish HaFeez 6:28 pm and the study was compliant with PRISMA systematic review guidelines
		Kirolos Michael 6:28 pm so this is a systematic review
		Kirolos Michael 6:28 pm everyone clear what a systematic review is?
		Emma Mackender 6:28 pm Not really (sorry)
		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 6:29 pm That’s right Jacob
		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 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 6:32 pm what are some other types of reviews? i think ive only come across systematic reviews?
		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 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 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 6:34 pm Danish HaFeez, Absolutely. these reviews are helpful at discussing recent trends in a speciality for example
		Kirolos Michael 6:34 pm Hadis Reyhani, Very good question
		Kirolos Michael 6:35 pm for a systematic review to be effective/valid, the inclusion/exclusion criteria must be selected a priori
		Kirolos Michael 6:35 pm that means “before” they run the search
		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 6:36 pm alright, let’s move to the methods
		Kirolos Michael 6:36 pm What was the population of interest?
		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 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 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 6:38 pm So just resections of low-grade gliomas with 5-ALA & no biopsies
		Kirolos Michael 6:38 pm Have a look at page 3 guys
		Kirolos Michael 6:38 pm this is what you should look for in a systematic review
		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 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 6:40 pm On to the results
		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 6:41 pm Everyone agree? Any other thoughts?
		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 6:42 pm All 3 of you are spot on
		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 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 6:43 pm In summary, low-grade gliomas (LGG) had low positive fluorescence, so most of them didn’t fluoresce
		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 6:45 pm but I agree, it feels a little out of place in the middle
		Kirolos Michael 6:45 pm Emma Mackender, could you elaborate a little more?
		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 6:48 pm Absolutely
		Emma Mackender 6:48 pm I’m assuming that’s a difficulty when producing a SR
		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 6:49 pm So the papers do fit their exact criteria, however the data from the papers is not heterogeneous
		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 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 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 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 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 6:54 pm Gagana Mallawaarachchi, does the above answer your question?
		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 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 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 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 6:58 pm Any strengths?
		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 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 7:00 pm Danish HaFeez, That’s absolutely right. I can see you’ve read this article very thoroughly
		Kirolos Michael 7:01 pm great with the strengths, anything else in terms of the methodology?
		Annabel Chadwick 7:01 pm they used the PRISMA checklist
		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 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 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 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 7:03 pm Good points Hadis & Tricia
		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 7:04 pm *fact
		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 7:05 pm only then can you undertake a forest plot
		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 7:06 pm okay thankyou, sorry i am new to this!
		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 7:06 pm as a summary
		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 7:07 pm Any weaknesses?
		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 7:07 pm They missed some big databases like medline/embasse?
		Kirolos Michael 7:08 pm Good point, they could have included more databases
		Kirolos Michael 7:08 pm We’ve already mentioned heterogeneity of articles
		Kirolos Michael 7:09 pm just out of interest, does anyone know how they could reduced the heterogeneity?
		Jacob Barnaby 7:09 pm n = 12 is a fairly low number of papers?
		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 7:09 pm stricter inclusion criteria?
		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 7:10 pm Annabel Chadwick, Spot on.
		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 7:10 pm would stricter inclusion criteria mean focusing on either retrospective/prospective studies?
		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 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 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 7:12 pm Bear in mind an SR is a review, it should present anything new etc.
		Kirolos Michael 7:12 pm Emma Mackender, it doesn’t matter. Anything that fits the critera really. That is all
		Kirolos Michael 7:12 pm in fact, this particular SR had a randomised-control-trial (RCT) included
		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 7:14 pm so in summary, has this study answered the question it set out to answer?
		Kirolos Michael 7:15 pm Any final thoughts?
		Jacob Barnaby 7:15 pm It doesn’t give a solid answer
		Jacob Barnaby 7:16 pm they allude to the idea that they need more evidence/”future studies” to give a better answer
		Kirolos Michael 7:16 pm Agreed
		Jacob Barnaby 7:16 pm But they are semi-optimistic about the future of the technique
		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 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 7:18 pm Danish HaFeez, spot on
		Kirolos Michael 7:18 pm Any other comments?
		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 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 7:19 pm as always, you can email me at kirolosmichael@gmail.com for any questions or suggestions
		Tricia Tay 7:20 pm Thank you for this session!
		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 7:21 pm thankyou
		Kirolos Michael 7:21 pm I’m very impressed by the discussion today
		Jacob Barnaby 7:21 pm Thank you for your time this evening
		Hadis Reyhani 7:21 pm thank you!
		Kirolos Michael 7:21 pm You guys have demonstrated great critical thinking skills that can be applied in many different ways
		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 Reply Thank you!