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dr_barrett's profile
PaedsHaemDoc
PaedsHaemDoc
PaedsHaemDoc
@dr_barrett

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PaedsHaemDoc

@dr_barrett

Paediatric Haematologist views are my own - RT not endorsements . Hate pseudoscience - main interest Leukaemia of infancy - daddy to 2 daughters ❤️. ENFP

Dublin City, Ireland
Joined August 2012

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    PaedsHaemDoc‏ @dr_barrett Apr 4

    #PANDA article by @ClareCraigPath Dec 2020 is a very confused commentary full of errors – it is an exemplar in clutching at straws & demonstrates; Poor understanding of PCR, basic definitions, basic math and poor logic ... my 🧵will explain Please Retweet & spread this exposepic.twitter.com/YXuVuTTy7h

    6:13 PM - 4 Apr 2021
    • 177 Retweets
    • 335 Likes
    • Toknell 🇸🇪🇸🇪 mikegill111 Andrew L. Croxford Phill DPhil Sue W. Chris Slane Diane Hanfelt Dave H 🏴󠁧󠁢󠁳󠁣󠁴󠁿 🇪🇺 Invoke Clause 8 (1320) 2covet
    23 replies 177 retweets 335 likes
      1. New conversation
      2. PaedsHaemDoc‏ @dr_barrett Apr 4

        Dr Craig tries to define “operational false positive rate” She makes a fair job of the “operational” part – involving the whole process But fails to define false positive rate – as we will see later this matters! She does not seem to know the definition so I will put it herepic.twitter.com/tAy00DNblx

        2 replies 7 retweets 49 likes
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      3. PaedsHaemDoc‏ @dr_barrett Apr 4

        False-positive rate – the chance that someone truly negative is labeled as positive – the denominator is all truly negatives (false positives and accurate (true) negatives.) The prevalence of disease in all a population of all truly negative people is ALWAYS 0% by definition.

        1 reply 3 retweets 40 likes
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      4. PaedsHaemDoc‏ @dr_barrett Apr 4

        Mathematically FPR has no intrinsic link to the prevalence of the test population. Now the first reasons for false positives is “profiling errors” She talks about populations with high false positives rates ...pic.twitter.com/GdzsCRPIfa

        1 reply 4 retweets 37 likes
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      5. PaedsHaemDoc‏ @dr_barrett Apr 4

        What @ClareCraigPath is initiating discussion on is the prior probability of the test population E.g no children in reception class in primary school will be pregnant ... but as we saw FPR is however NOT intrinsically affected by low prevalence rates it the test populationpic.twitter.com/LPpWYqqfsZ

        2 replies 5 retweets 35 likes
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      6. PaedsHaemDoc‏ @dr_barrett Apr 4

        As the FPR is only based on the rate of false detection in the negative population. So “poor profiling” by selecting low prior probability (low suspicion) population does not raise the FPR - (I will come to what it DOES affect later)pic.twitter.com/ZVs02TsZ4Y

        1 reply 5 retweets 36 likes
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      7. PaedsHaemDoc‏ @dr_barrett Apr 4

        In the middle of this section, Clare makes a huge claim with no evidence. That patients in their 20s had a high false-positive rate. To “prove” this she claims lack of spread from younger to older age groups in August. This is a poor argument logically and factuallypic.twitter.com/FUz5kfUuHa

        1 reply 4 retweets 45 likes
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      8. PaedsHaemDoc‏ @dr_barrett Apr 4

        First of all it assumes that spread is a Fait accompli - which is not the case In fact when prevalence is low this far from the case – it is during low prevalence (like in August) that “shielding” and cocooning works best – as john Ionniadis unintentionally showed.@DrDomPimentapic.twitter.com/emvPg6JwGX

        1 reply 5 retweets 34 likes
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      9. PaedsHaemDoc‏ @dr_barrett Apr 4

        The other reason it’s a poor argument is that in August virus did show evidence of spread to older age groups. @Dr_D_Robertson was showing this at the time .. and the trend continued, unfortunately ... 👇pic.twitter.com/vWiZHG9JlP

        1 reply 5 retweets 36 likes
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      10. PaedsHaemDoc‏ @dr_barrett Apr 4

        At this point – it may have occurred to some that Clare seems to have attached to prior probabilities as she has confused the CONCEPT of false-positive rate and positive predictive value/ false discovery rate… As we will see from a calculation she does later this is the case…

        1 reply 5 retweets 40 likes
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      11. PaedsHaemDoc‏ @dr_barrett Apr 4

        At this point – it may have occurred to some that Clare seems to have attached to prior probabilities as she has confused the concept of false-positive rate and positive predictive value… As we will see from a calculation she does later this is the case…

        3 replies 3 retweets 29 likes
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      12. PaedsHaemDoc‏ @dr_barrett Apr 4

        Its not my job to fix Dr Craigs misunderstanding – but I will do the opposite of a strawman I will #ironman her argument – talk about false discovery rate FDR (1 – positive predictive value PPV)pic.twitter.com/T29HjQeEex

        1 reply 6 retweets 43 likes
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      13. PaedsHaemDoc‏ @dr_barrett Apr 4

        The FDR – rate of false positives amongst all positive tests; it’s a post-test probability. Unlike the False positive rate – it IS affected by underlying prevalence (bad "profiling") How does Clare’s case hold up now …pic.twitter.com/9xL58Cx2I0

        1 reply 5 retweets 30 likes
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      14. PaedsHaemDoc‏ @dr_barrett Apr 4

        Her argument is certainly improved by the use of the correct terminology that Dr Craig appears to never hear of … But what have we seen in low prevalence situations with Sars-Cov-2 testing …. FDR should be high here EVEN with very high SPECIFICITY Let's look at some examples

        1 reply 3 retweets 30 likes
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      15. PaedsHaemDoc‏ @dr_barrett Apr 4

        False discovery rate – SHOULD be highest in regions of very low prevalence New Zealand – famously low prevalence of COVID19 So low PPV / high FDR right? Why do we know it is not poor 1 –Only 4% of NZ cases have no sourcepic.twitter.com/4db2IVF2XU

        2 replies 6 retweets 35 likes
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      16. PaedsHaemDoc‏ @dr_barrett Apr 4

        If we can see where the positive tests (smoke) are coming from – a clear cause of a burning fire we can be confident the cases (smoke) are real. I mean smoke can always be from a smoke machine right ... but don't make that stretch when we can see the flames.. see below 👇pic.twitter.com/C1cgEJw8qS

        1 reply 4 retweets 31 likes
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      17. PaedsHaemDoc‏ @dr_barrett Apr 4

        2-After the fact of the diagnosis – NZ was able to near full sequence the genomes for 649/733 or 88.5% , of PCR positive cases … Full viral genomes don’t come from false-positive PCRs … Suggesting a PPV at LEAST 88% in a VERY low prevalence setting LIKELY FAR HIGHERpic.twitter.com/PrGCUVLmfc

        4 replies 7 retweets 39 likes
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      18. PaedsHaemDoc‏ @dr_barrett Apr 4

        PaedsHaemDoc Retweeted Rick Ramirez

        This despite very sensitive testing criteria employed by NZ. NZ is employing precautionary principles – the WANT to find cases "Ct values" are Cannard used by @ClareCraigPath ... but New Zealand maximizes sensitivity by using very high Ct cut-offshttps://twitter.com/Rick82Ramirez/status/1372787049565093894?s=20 …

        PaedsHaemDoc added,

        Rick Ramirez @Rick82Ramirez
        Per New Zealand government... A 40 cycle threshold for their PCR tests 😳 “We report that the PCR is "SARS-CoV-2RNA detected" when two different PCR targets (regions within the SARS-CoV-2 genome) have Ct  values below 40 cycles” https://fyi.org.nz/request/14250/response/54374/attach/html/7/OIA%20Response%20Andre%2012.02.21.pdf.html … https://fyi.org.nz/request/14250-covid19-pcr-cycle-threshold …
        1 reply 4 retweets 34 likes
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      19. PaedsHaemDoc‏ @dr_barrett Apr 4

        Clustering of cases in subgroups eg: exposed / symptomatic– even in low prevalence setting also increases confidence in positive predictive value REACT May 2020 study from UK (0.13% +ve) – a covid contact led 24 x increase in the chance of +vepic.twitter.com/MkRdkpNQM5

        1 reply 3 retweets 26 likes
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      20. PaedsHaemDoc‏ @dr_barrett Apr 4

        The strongest risk factor for a positive test – was contact with a positive case …. The odds ratio of 24. If your wife tests +ve on Monday you can be very confident your +ve on Wednesday is real …pic.twitter.com/wurSjnoghi

        2 replies 4 retweets 31 likes
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      21. PaedsHaemDoc‏ @dr_barrett Apr 4

        The ONS also provides additional evidence that on their survey that their very low rate of positives represents true positives - thanks @DrNickB_ObAnaes for point this out ... it explained here - though admittedly hard to follow IMHOpic.twitter.com/mHgVLdge2j

        2 replies 3 retweets 24 likes
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      22. PaedsHaemDoc‏ @dr_barrett Apr 4

        Basically, the point is that several risk factors for positivity independently associate with positivity in the post-test setting. I try to explain it below. This is because its specificity is VERY HIGH - the PPV will be LESS affected by pre-test selection....pic.twitter.com/q6gjc2sH6k

        1 reply 3 retweets 23 likes
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      23. PaedsHaemDoc‏ @dr_barrett Apr 4

        The next section @ClareCraigPath now attacks the PCR test itself ... I could simply refer you to excellent pieces by @MackayIM on the matter https://virologydownunder.com/the-false-positive-pcr-problem-is-not-a-problem/ … and this apt "primer" on PCR itselfhttps://virologydownunder.com/the-mechanics-of-the-polymerase-chain-reaction-pcr-a-primer/ …

        1 reply 5 retweets 32 likes
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      24. PaedsHaemDoc‏ @dr_barrett Apr 4

        Mistaken Identity ... @ClareCraigPath pulls out a study from 2006 in which Human DNA was mistaken for another different coronavirus ... This occurred less than 1% using a nested PCR technique.... but going back to a single 15-year-old study is CHERRY PICKING ...pic.twitter.com/rcZ1BeYXVz

        1 reply 5 retweets 30 likes
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      25. PaedsHaemDoc‏ @dr_barrett Apr 4

        Of course, @ClareCraigPath is not entirely consistent on relying on studies from different coronaviruses when it does not suit her viewpoint ... that said as I will show modern techniques and validation shoot holes in this cherry-picked example....pic.twitter.com/F5jjKnOj5U

        1 reply 3 retweets 23 likes
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      26. PaedsHaemDoc‏ @dr_barrett Apr 4

        First of all @ClareCraigPath mention of billions of letters of code is disingenuous when it comes to PCR - mainly because PCR products are designed to be short usually a few hundred base pairs - if one primer misaligns the other primer has only a few hundred BP to find a matchpic.twitter.com/6ncVD8x4mw

        2 replies 5 retweets 24 likes
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      27. PaedsHaemDoc‏ @dr_barrett Apr 4

        This is much better understood with @MackayIM https://virologydownunder.com/the-mechanics-of-the-polymerase-chain-reaction-pcr-a-primer/ … "primer on PCR" but I try to simplify this point below .. 👇 Basically, the time length of the elongation phase limits the PCR product length ... which adds specificity even if primers non-specific matches ...pic.twitter.com/2rn3OLLiLv

        1 reply 4 retweets 29 likes
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      28. PaedsHaemDoc‏ @dr_barrett Apr 4

        Apologies Twitter has made me publish this early due to length of the thread .... bear with me if you are seeing this incomplete thread...

        1 reply 2 retweets 23 likes
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      29. PaedsHaemDoc‏ @dr_barrett Apr 4

        Clare is disingenuous referring to 3 billion letters of code In truth, the primer pairs much find “near” matches within a few hundred base pairs to amplify a product - additionally products of the wrong length can be spotted on QC melt curves at the end of the PCR examples👇pic.twitter.com/4zPx6ZHjGN

        2 replies 6 retweets 28 likes
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      30. PaedsHaemDoc‏ @dr_barrett Apr 4

        The other reason this won't be a problem from most PCR protocols that most include a probe to positively identify the PCR product - see below for an explanation 👇. Basically not only must the PCR amplify - it must amplify the correct product.pic.twitter.com/yubRSl5Pqh

        1 reply 4 retweets 26 likes
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      31. PaedsHaemDoc‏ @dr_barrett Apr 4

        Next @ClareCraigPath now claims that again for another Coronavirus was found to be mistaken by PCR for different viruses This again is a cherry-pick from 2006 on a different coronavirus - but here Dr. Craig is WRONG - the study did NOT show picking up of another virus ...pic.twitter.com/QkitKh2abl

        1 reply 4 retweets 34 likes
        Show this thread
      32. Show replies

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