Page 1

mercer county community health assessment report 05 12

donde reportar una fuga de agua 05 15

3 SENTENCE SCHOLARSHIP ESSAY 08 25

ios uitableviewcell custom background image 05 15

EAST CAROLINA UNIVERSITY COLLEGE APPLICATION 09 03

afrikaans evolution writers 1 febmarch 2020 05 05

CAMBRIDGE INTRODUCTION CREATIVE WRITING REVIEW 08 25

how to write an apa evolution writers abstract 05 04

essay uk university 05 03

UNIV OF SOUTH ALABAMA ADMISSION REQUIREMENTS 09 02

hunterrr movie review rajeev masand blind 05 12

UNIVERSITY CLUB REVIEWS 09 02

audit report writing class 05 10

download novel life of pi pdf 05 13

reasons for imperialism essay 05 12

DATA INNOVATION PROJECT UNIVERSITY OF SOUTHERN MAINE 09 03

CV OXFORD UNIVERSITY 09 04

rabid love movie review 05 13

three ancient writing materials 05 05

SOCIOLOGY PAST PAPER PUNJAB UNIVERSITY 09 03

kaplun foundation essay contest 2018 nfl 05 10

articulo 1 de la constitucion politico colombia analysis essay 05 09

UNIEKE CV LAYOUT 09 03

news of the world reporter dead in car 05 14


blue pacman ghost pill reports australia 05 10

WHAT ARE THE 6 TRAITS OF GOOD WRITING 08 24

urdu writing website 05 08

sterling superkings menthol review of literature 08 19

cat climbs on reporter video 05 13

pop music research paper 05 08

looking for someone to make dissertation introduction on gun control 05 09

UNIVERSITY DODGE REVIEWS 09 04

speech improvement 05 15

DEVOTIONAL WRITERS NEEDED 08 25

cover letter entry level driver kids 05 14

research evolution writers on self help groups in india 05 05

microsoft excel 2018 functions and formulas quick reference card pdf 05 14

essay generator app 05 02

argumentative research evolution writers questions 05 03

ristorante la colombaia aversa prezi presentation 05 11

HOW TO DO A BIBLIOGRAPHY UNIVERSITY 09 02

PRESENTATION EXAMPLE UNIVERSITY 09 02

religious freedom essay titles for of mice 05 14

teachers day essay in hindi short 05 12

module c into the world essay game 05 09

PUBLIC UNIVERSITIES ADMISSION 2019 09 02

what it means to be catholic essay contests 05 12

arrogance definition essay ideas 05 08


SHORT COURSES IN UNIVERSITY OF TORONTO 09 01

eu legislative proposals for country by reporting illegal immigrants 05 13

College of Physicians and Surgeons ​I think it's very difficult to fully appreciate the implications of the images in front of you. They will make us think differently about the disease, they will make you communicate differently about the disease. The images in front of you allow me to communicate to somebody outside of this room, and tell that individual that this patient has a 0.3cc prostate cancer just to the right of the midline; it exhibits 8mm capsular abutment, which gives it about a 30% chance of capsular invasion. It has picked up a blood supply situated in the midline and is limited to the peripheral zone. I could speak to Laurence Klotz in Toronto; he could be in theatre without the images. I could tell him to put the patient foley catheter in, get the needle behind the catheter, advance the needle parallel to the Denonvilliers' fascia 5mm anterior to Denonvilliers' fascia and deploy the needle 1.5cm in the prostate. He would get a direct hit. Just to be sure, I'd say move to your right by 5mm, do exactly the same and redeploy that needle. It is very likely that you would get two full chambers with about 5 to 7mm of cancer, and this one would be very likely to contain pattern 4. This is a completely different world that we are entering. This has been an extraordinary week. The NCCN - for the first time ever - have suggested some of their sentences that imaging now will play an important role in the diagnostic process of prostate cancer. The same week, NICE, probably the most stringent evidence based body in the world, have rejected both PCA3 and PHI. The fact that PCA3 and PHI were rejected is not the interesting bit of the story, it is the way in which they were rejected. And they incorporated clinical assessment and MRI as the comparator. And by doing that, they implicitly assumed that MRI has become a standard of care. And by doing that, they make it almost impossible - as I will illustrate in just a second - for any biomarker to achieve any cost effectiveness. In this 82 page summary, which is on the public domain, you will find a number of tables, and what you will see here... (so this is clinical assessment, hasn't come through very well,) this is PHI, PCA3, PHI, PCA3, and the goodness here comes in the reduction of unnecessary biopsies, of course they are assumed in the model. But the benefit only really comes out when you start introducing MRI to it, you see the enormous reduction from 800 to 900 biopsies here to 500. So once you bring MRI to the model, the model changes significantly. And their conclusion was: In a maximum acceptable ICER of 37000 pounds per QALY gained, all iterations suggest that clinical assessment plus mpMRI dominates all other strategies in diagnosing clinically significant prostate cancer. How are we going to use imaging? We've got two evidence based bodies, both of which are completely unconflicted in a way that Laurence suggested. One of them is telling us to use imaging, and the other is actually implicitly suggesting that imaging has become a standard of care. What about ruling out clinically insignificant PCa? That's the first draw that we have. And that takes us to the first level one bit of evidence. It comes from Rome, is Valeria Panebianco here today? Well, this is an extraordinary paper that appeared about two months ago in an obscure journal and hasn't had much interest raised, but it was quite extraordinary. So, men from Rome, over a thousand of them were randomized for MRI based diagnostics strategy vs the standard of care, which is the TRUS based diagnostic strategy. 570 men went for MRI, and 570 men went to TRUS biopsy. And in red is where the randomization is complete, below that they were separated to different areas, so they are not balanced groups. The first thing to notice is that if you are in the business of detecting PCa, and you are not using MRI then you are underperforming by 100%. Most randomized studies held detect 10% differences, this is 100% difference in the detection rate of PCa. 72% if you are randomized to the MRI group, 38% if you weren't. If your TRUS as negative, and your MRI was negative, the rate of PCa detection was about 30%. If your TRUS was negative and your MRI was positive your detection rate of PCa went up to 88%. So all the prior probabilities here are confirmed by the MRI, not the TRUS biopsy. What if your MRI was negative? Well, 29% exactly the same as I showed you. If your MRI was positive in the first round, then you had a 93% chance of having PCa. So you get 9 out of 10 chance of having prostate cancer declared if your MRI was positive into that arm of the study. That's already level one evidence in a thousand men in a randomized study. For me, and for this question in terms of ruling out clinical significant disease, the most interesting bit of the story was this: None - that's zero percent - of 130 men with a negative MRI had any pattern 4 or 5 identified on a saturation biopsy. If your MRI is normal, you can't have a targeted biopsy, so they did a 48 needle saturation biopsy on the negative MRI's, and failed to identify any single person with anything that might be called clinically significant disease. So: Negative predictive value of 100%. And this is what they mean by the "normal" test, this is a PSA of 6.2 very low PSA density because the prostate measures about 80cc. and this is the normal MRI that they describe. This is a Siemens magnet you see (in a minute I'm going to show you data from a Phillips magnet). Doesn't matter what


platform, or in what country, or in what city you are diagnosed, the results are all very similar. And this is the normal MRI and Panebianco's statement would be odd if it were the first time we'd seen that. In Rotterdam, in a different series, we saw exactly the same: If you have a normal MRI (PI-RADS 1 or 2), the chance of having clinically significant disease in an admittedly small group, was again zero. One more because I collect these zero's: This is the Nijmegen group, an AC population of patients being re-classified. If your MRI was negative and thus declared normal, your chance of having Gleason 4 or 5 was zero, if your MRI was declared normal. So another, once again, negative predictive value of 100%. They're not pretending that this is going to be 100% when it plays out, but it's going to be very close to it. And if all you've got is no disease or Gleason pattern 3, you can rule out Gleason pattern 4 or 5 with 95 or 100% certainty, then you confirm population that don't have any additional risk of dying. So they die on the same date as somebody without a Gleason pattern 3. So you identify a population that will not have any reduction in life expectancy as a result of their underlying PCa, should a PCa be present. What about ruling-in disease? Ruling-out disease allows you to avoid a biopsy, and I suggest now that we have a pretty strong evidence that allows us to do that, what about ruling-in disease, if a man has clinically significant disease, how can we maximize the chances of detecting that? Here we have level 1 evidence, and was published in this very week, this is why this week is critically important, this is the Pinto group at NIH, this is a summary of their many publications that have appeared before in smaller cohorts, so this is the full cohort published now, from about 2008 onwards. It is not a randomized study, we don't need a randomized study to achieve level 1 evidence in a diagnostic study. This is a start compliant study equivalent for a diagnostics study. About the same number of men, about a thousand (these are big numbers), and this is men with lesions, so men without lesions were taken out of the study, we don't know anything about them. They were the group of men that had no Gleason 4 or 5 in the Panebianco group. And we had a cohort in the end of just over a thousand patients. There were two key analysis in this paper; one was targeted vs 12-core biopsy. Targeted lesions were allowed two needle deployments, and everybody got a 12-core biopsy by an independent operator that was blinded to the location of the target. The averaged detection rate was low, which is interesting. This is largely a re-biopsy group, the Panebianco group was a biopsy naive group, so they were a slightly different population. The overall detection rate was the same for both strategies, two needles vs 12 needles, creating the same number of cancers. But very importantly the targeted group with two needles identified 30% more patients with clinically significant disease. Put the other way: If you just did the 12-core TRUS biopsy you would miss 1/3 of patients with clinically significant disease. And if you did the targeted you've got an increased yield of the target or after, but you also reduced - by 20% - the proportion of patients you identified with clinically insignificant disease. So targeting is: Fewer cores, more cases of clinically significant disease, and fewer cases of clinically insignificant disease. The other key analysis was targeted alone vs. targeted plus TRUS. There is a big debate at the moment about whether we needed to do targeted plus random biopsies or if the targeting is efficient. And this is the best data we have to form that debate. The debate isn't finished, but this points very much to the direction that targeting is all we need to do. If you had to biopsy 200 patients with a TRUS in addition to the target to identify one patient with clinically significant disease. So you have to do a lot of work (200 times 12 needle deployments) to identify one additional patient with clinically significant disease, and for every patient you identify of those 200 you are going to identify 17 patients with low risk disease. So you're going to have to accommodate some degree of overtreatment. One in five rate of overdiagnosis for one in 200 rate of identifying an additional case of significant disease. And then there is this thing, which I think is very interesting. There are a lot of ways in looking at performance of accuracy. The AUC probably incorporates most the evidence we are after. In fact, on almost every criteria is targeted biopsy that is superior to TRUS alone, and very importantly, to targeted plus TRUS together. And the summary data is there: The area in the curve shows for targeted alone (just two needles) is 0.73 versus 0.59 for sextant alone, and 0.67 for sextant plus targeted. So we can see where the goodness lies. An efficient allocation of one or two needles to the target to maximize the yield of clinically significant disease and address the issue of overdiagnosis. This is our own data, published in 2012 in J. Urol. It's important because it differs from the Pinto data probably in where we declare a lesion. There are only a hundred patients (only 10%) in the Pinto group that were declared free of a lesion. So the threshold in the USA in general and the NIH in particular is very low for declaring a lesion a lesion. In Europe we tend to have a higher threshold for declaring a lesion, and that means that the yield of a targeted biopsy increases, but also the proportion of patients who test negative increases. This is 138 men with lesions (like the Pinto population, not like the Panebianco population) and they had targeted biopsies versus a 5mm sampling via a transperineal template biopsy. This is one patient: He had a lesion at 12 O’clock, he also had 5mm sampling, and this typical patient did have 1 and 4mm CCLmax, Gleason 3+4 and all non-targeted samples were negative prostate cancer. And this is the difference in work load from the targeted versus the non-targeted approach: 900 needle deployment versus 7000 in


this cohort of just over a hundred men, 5 needles per patient versus 30 needles per patient, a sampling density of one per 10 cc vs about one per cc and already you can see that the detection efficiency per needle deployment is much greater for the targeted biopsy than the random, as you would expect. The data is similar in terms of detection to Panebianco, our overall detection rate was 78%; if I biopsy you, you have a 4 out of 5 chance of having prostate cancer, and a 3 out of 5 chance of having clinically significant prostate cancer. Not similar to the Panebianco group, but much greater in the NIH group, largely due to the result of their threshold population issue. And again, just to show you that there is a consistency in the data: if you compare template biopsy (lots of needles) to a few (usually more than one) to the target you had no significant difference in the proportion of clinically significant disease detected. And you had a reduction in the number of patients with clinically insignificant disease that contributed in the diagnosis, too. This has implications for the way that we approach patients, this has huge economic significance, and we should be able to avoid by using MRI traditionally about a third to half of a million biopsies per year in the EU alone, and probably more in the United States. There are huge monies to be saved. This is just very recent comparing using surveillance versus treatment for men with significant disease to aggressive treatment. 1.3 billion per year costs savings anticipated. Just imagine if you didn't diagnose those patients and didn't have to do AS on those patients, the savings would multiply by many many times. In summary: We have level 1 evidence that is of high quality and in sufficient volumes to make some statements. There is very little benefit in subjecting a man with a normal MRI to a biopsy. It has to be a good MRI, has to be well read, has to be verified - we have to know that it's a good value. And there is plenty of evidence now to support that. An MRI should be done before a biopsy in all men if you wish to diagnose more cancer, if you wish to miss fewer significant cancers and if you wish to diagnose fewer men with insignificant cancers, or if you want to do a bit of all three. If you want to diagnose fewer men overall, but enrich that population with clinically significant disease and diminish that population with clinically insignificant disease then there is only one way for it. Thank you. Columbia Law School.

https://Dissertation.space

IQRA UNIVERSITY SAMPLE TEST PAPER FOR ENGINEERING  
IQRA UNIVERSITY SAMPLE TEST PAPER FOR ENGINEERING  
Advertisement