Daniel Williams:

Hi, everyone. My name's Daniel Williams, senior editor of Industry Content at MGMA. Welcome to today's webinar, 'Driving Test Standardization That Meets Provider And Patient Expectations: One System's Journey. Thank you for joining us. We'd like to thank Cepheid for their sponsorship. Please visit their website at cepheid.com/mgma to learn how their game-changing RT PCR platform can help your organization increase practice efficiencies, patient satisfaction and revenues.

Please see the slide for available credits for the live and on-demand experiences. To claim all credit types, you must complete the session evaluation following the webinar. We highly encourage interactivity in our digital events, so please use the chat button to talk to your fellow attendees and the Q&A button to ask questions for the presenter. Any additional resources such as the slides and session evaluation can be found in the learning management system where you access this program. The education for this session will now begin.

In today's webinar, Mary Hammel, system point of care manager at UC Health will discuss how UC health improved patient satisfaction and standardized care through selecting the right platform for respiratory testing across dozens of sites. Mary, I know you've got a lot of great information to share, so I'm going to turn this over to you now.

Mary Hammel:

Thank you, Daniel. Thanks for having me.

Hello, everyone. My name is Mary Hammel. As Daniel said, I'm a laboratory scientist at UC Health in Colorado. Today we're going to be talking about driving test standardization that meets both provider and patient expectations and we're going to be talking about my system's journey through that. Today, my disclosure is that Cepheid has given me an honorarium to bring my experience to you today.

We're going to talk about point of care evaluation strategy for choosing new platforms across many clinics in the outpatient setting where we're going to view my hospital system decision to remove antigen testing for respiratory illness and Group A Strep. Then we're going to review several considerations that help guide our hospital system choice of platform for respiratory testing.

Here at UC Health, we're in Colorado, we're spread all across the front range. Our southern hospitals start in Colorado Springs down south, and they extend all the way up to the Wyoming border in our northern region. They consist of 12 hospitals, 11 freestanding emergency rooms, and then more than 90 clinics. In those clinics we've got primary care, specialized care, urgent care, I have 22 urgent cares, and those are all included. When I talk about clinics, I'm talking about all of those different locations. Primarily today we're going to talk about those clinical locations I mentioned, so primary care and urgent cares. Those are all waived sites here in our UC Health system. We do actually have over 130 now.

In 2019 I was asked to give oversight to the laboratory point of care that was being done in these areas. Prior to my oversight, I wouldn't say it was a free for all, but definitely each region had its own way of doing things. We didn't have any kind of standardization in terms of what platforms we were using for all the testing. It wasn't just respiratory testing, but it was monos and urinalysis. Basically for every type of test we did, we probably had five or six different vendors across our entire system. What that meant too is that we weren't using the same procedures, we weren't doing the same things at the same time, and we also did not have any kind of standardization with vendor contracts at all.

In late 2019, the first thing we started looking at was standardizing all of that testing first and foremost. Specifically for flu, strep and RSV, we noticed that we had antigen tests in some places and others we were doing immunofluorescence, in others we were doing isothermal nucleic acid amplification and in others we were just doing traditional PCR.

We began an evaluation process that really centers around the things that are important to our point of care program, both in the outpatient and our acute side of the hospital setting. We always look at, does this test help us identify the right patient? Are we doing the right test on the right patient. Then second the right test. Is this the test that we want to use for this population of patients? Also, the right result. Are we getting the right result and the first time. Are we getting it the first time, especially in this outpatient location. Historically, point of care has always been that, "Well, it's just sort of a screening test. We're not really sure, let's send it to the lab to be sure."

We really wanted to move away from that model and give our patients at that first point of contact, the right test at the right time. So to do this, we primarily looked at three different things, in this order. We looked at quality of the test, we looked at the cost of the test, and then the ease of use. I get asked a lot about why doing it in that order, wouldn't we want to look at the cost first, but truly, especially with point of care, there are so many tests out there, and there are some really cheap ones, and if you're strictly going that way, you're completely missing all of these other things like the right patient, right test, right time, first time. We always start with quality and we go down from there as far as our evaluation at UC Health.

Of course, when I was given this assignment, it was late 2019. We started putting together spreadsheets, comparing everything, and then we went straight into Covid. So immediately my whole focus had to shift into looking at the platforms that specifically offered Covid for respiratory testing. I was asked by my system command to put aside all the other tests I was evaluating that didn't have to do with respiratory or strep. We began comparisons of performance between the antigen testing, the IFA, the isothermal PCR, and the traditional PCR for the tests that we could get that were actually doing Covid. I don't know if you remember at the time, not everybody was doing it. There were only specific vendors and if you weren't already doing that test, you weren't going to get it. We had to take what we had and start evaluating that.

One of the first things we looked at specifically for Covid is we started comparing our isothermal PCR to our regular, traditional PCR. What we found, and I'll discuss more in the next slide, is that the isothermal had missed 20% of the positives that our clinical lab or our main lab was able to pick up with our Cepheid and Roche platforms that we already had, that we had just started running Covid on. The other thing with strep that my system command wanted me to take a look at that they had already started looking at, because our antibiotic stewardship committee was kind of really pushing us toward this, was the impact of poor antibiotic stewardship as it relates to strep testing. So that is why strep got included when we started comparing PCR against either isothermal PCR, antigen testing. We were going to include this in our entire workup.

One of our first studies that we did compared the Abbott IDNow, which is the isothermal PCR, to our Cepheid GeneXpert Xpress and the Roche cobas 6,800 that we had in the lab. As COVID went down further, we had several other platforms, but these were the first two that were brought up besides some of our home brew technologies.

As you can see, we did realize that the labs, sorry, the clinical lab was picking up 20% more positives than the isothermal PCR. To give you a little bit of background, this was done in our largest emergency room at the Anschutz campus in Denver, Colorado. So we had a huge volume of patients. These were all a hundred percent symptomatic patients. At this point we were not doing any asymptomatic testing at all, so a hundred percent symptomatic patients. I actually went up there and made sure that the techs down in the emergency room that are doing the collections and then the texts that were in the laboratory comparing the Abbott IDNow to the platforms were doing it correctly, that we were following the IFUs specifically for each platform to the letter, because I wanted to make sure that these were the most accurate results we could get.

System command took a look at this and they decided, based on this information, that no matter what platform we ended up moving to, it was going to be traditional PCR because they wanted to make sure that whatever tests we were offering the patient from the primary care sites, the urgent care sites, freestanding [inaudible 00:09:48] and hospital, they really loved the idea of giving our patients that same testing across the board.

Of course, the next thing we were going to look at, when we were comparing and evaluating platforms, was the cost. We wanted to know if the reimbursement was solid for PCR. At the time everything was EUA, government was paying for a lot of things, and so we definitely had to go off of our best guess about what that would look like down the road. I currently get denial reports all the time, once a week actually, for all of the laboratory testing, not just this. Our reimbursement is solid for PCR here in Colorado in how we're charging for this. That was good to know. It was sort of one of those guesses when we went in, especially since the government was paying for everything in the beginning, but now we're still seeing that it is a very solid reimbursement for us.

The other thing that we need to look at for cost is that we needed to consider the cost of confirmatory cultures and the cost of repeat visits. Repeat visits is a little bit harder, and right now I'm gathering data on that and hope to have that information to give in a different webinar soon. Confirmatory culture was interesting. I had no idea, for our system, how much that cost. A culture for us started at $150 and that was before a positive workup so before we isolated the beta hemolytic strep and did any kind of latex agglutination testing on it. After those things, it could run up close to $250 for that test. We were doing those on a hundred percent of pediatric antigen negative tests, we would reflex to a culture. There was definite cost there that we really hadn't considered before this time.

Also, ease of use. We put staff in front of a bunch of different platforms to see which ones they felt good with. Of course, the staff, they felt like it was easier and faster for the Cepheid method than some of the other methods. That was kind of more of a one step thing and it was a lot less room on their counter than having several machines and you could run more at once, so they really liked that.

One of the big concerns though was the length of time to result and how was that going to affect our workflow, both for Covid testing and for strep. Although, right now, I'll tell you anecdotally, I didn't get any pushback for the length of the Covid test. I mean, it was what it was and we had to do it, but I got a lot of concern from providers about how long it was going to take that extra 20 or so minutes, how long was that going to keep the patient in clinic, whereas they could have just discharged them.

Two things about that. Number one, we didn't see any change of time in patients spent in clinic. There's a couple of reasons for this, but I think anecdotally when people think, "Oh, it's a five-minute test, we can get them out faster." Really, truly, if you look at the time spent before we were doing PCR and after we were doing PCR, there was no change to the time the patients actually sat in the clinic, whether we had a five-minute test or whether we had a 20-minute test, it wasn't changing anything. Especially during Covid, however, we designed a workflow that, they don't use in every single clinic, but they use in a lot of the urgent care clinics and some of the real large primary care clinics and also the primary care clinic where I take my kids.

What they will do is we have a health app, a patient portal app where the results will go straight to the app and sometimes I've been sitting inside the doctor's office when the results come, but many times the provider will talk to the patient and say, "We're going to run this test for you. If it comes back positive for strep, we're just going to send a prescription to the pharmacy that you've already told us that you want. We're going to send that in. We're going to talk to you about care for yourself, if it is positive, but if it's negative, these are the things I want you to look at. Here's the self-care and here's what I when you to come back if your symptoms persist."

At that point, they discharge the patient and the patient goes. Meanwhile, the test is being run in the background and then when it's done, it'll go to your app. Many times I've been in the parking lot when the result's done and then my prescription is called and I just headed straight over to the pharmacy. I have two kids, 11 and 13, so they do this a lot. That was one of the unique workflows they developed during Covid that we were able to use. They use this also for Covid, but really the concern from most of the providers was for strep. Those are some of the workflows that we designed. Ultimately, we did not see a change in time. Patients are not hanging out longer in the clinics because of the PCR testing overall, whether we're talking about respiratory or strep.

Some of the other things we looked at, especially for right patient is; is the test interface. We'll talk about this in another screen in a little bit too. Having an interface test accomplishes a couple of things. It makes sure that that test result gets in the patient chart. If you're even a CLIA waived or a CLIA certificate of compliance, there are rules surrounding those results and how they're reported and do they have reference ranges attached and can you tell where the testing was done. There's a whole host of rules that you have to follow for patient reporting. One of the things when we started looking at clinic reporting before Covid is that we were not interfaced in most instances with any of the machines that could be interfaced. We have since started a process to interface those tests and it's been amazing. The revenue capture for interfacing them has been, in some cases, up to 88%. That was for hemoglobin A1C, not this test, but it's really incredible.

The second thing that's important is now these results are in the patient chart for follow-up, for the continuity of patient care and also so that we can drop a CPT code and get reimbursed for that, that wasn't happening either. It was really important to us that whatever test we chose for respiratory testing and for strep testing, that we could also interface this and no longer just have a dipstick because we had realized all of that revenue capture and quality that we were missing without having those interface tests.

We also wanted to make sure that interfacing fit easily into our workflow on how to identify the patient properly. Do we have the right chart stickers? Because obviously we're not going to be there in the room scanning the patient armband as though you had a glucose machine. We wanted to make sure we had the right workflow and that whatever platform we chose would support that workflow in order to identify the patient correctly. Again, right test. Is this the most appropriate test to use for this patient population? Where we were still only testing for symptomatic patients and so we wanted to make sure that we had the best test for this particular patient population.

Right result. Could our providers act on this test result with confidence? What we didn't want them to be saying anymore was, "Well, this antigen test, you know what? Historically it could be 20 to 30% wrong. If it was negative, it might be positive, so let's either send it to the lab to be sure, or let's do a culture to be sure it's really negative." Or even, "You know what, it's negative, but your symptoms look like they're positive, so let's just give you antibiotics anyway." That's what was happening. We wanted to take the question out of it so that the providers could have confidence in what tests they were using the first time and give the patient that confidence like this is really what's wrong with you and this is how we're going to treat it.

Again, that kind of ties into the last one, the first time. Is this test going to reduce retesting in the clinical lab and then retesting a patient because they have to come back because they're still sick?

In the end, somewhere in the end of 2020, I think it was October, we made our system decision to go with Cepheid Xpert Xpress and we decided to use that fourplex cartridge, the FLUVID cartridge, and then also the Group A Strep cartridge. It was in the spring or in the summer of the next year that we did add just the Covid only cartridge. As we came out of that influenza season, providers did want to just run Covid. We do give them the option, based on symptoms, to either run the fourplex, which we call the FLUVID, or the Covid-only test. We'll get a little bit into that too.

There are additional considerations to bringing in PCR testing to your clinics. It's not super easy. There are a lot of considerations you have to look at and we'll go through these. The first one was biosafety. It's not as big of a deal now, but at the time there were many laboratorians were like, we can't give PCR to waived locations. It was not a thing. My background is as a microbiologist, and so even I was a little bit hesitant. The PCR that I remember doing was in a clean room walking around in a circle, so not to contaminate everything. In my mind, how could we just put it in a waived machine and give it to non-laboratory staff to run? It was an awkward feeling, to be sure.

The first thing we did was go through the CDC recommendations for PCR testing at the point of care. Even during Covid, for waived testing, the CDC was recommending beyond whatever normal PPE you would wear, they recommended at that time a splash shield. They did not recommend it being done under a hood. Again, laboratorians were a little weirded out by that, and I think still I get a lot of questions about; what you don't run it under a hood? No. No, we don't. There's no aerosolization and we were only using nasal swabs, not nasopharyngeal swabs, so that helped with keeping that aerosolization down. The staff at the time they used PPE, they had splash shields, they did not have biological hoods.

The other thing we were worried about was contamination, right? If you know anything about PCR, back in the day, contamination was a real issue. If you contaminated something, your entire lab was down. There were amplicons everywhere and the cleaning, it was just a lot. We have memory of that and so we were worried like what happens if someone contaminates a machine? What are we going to do? I had an entire procedure written ahead of time to address a contamination protocol. I've never used it. We've never had a contamination, knock on something, but it's absolutely never happened. I'll discuss a little bit about the software that we have with Cepheid, and C360 is what it's called. It really helps with this. We'll talk about that in a little bit.

One of the other things that really helped us through, and we are still using these, was the guidance that we gave providers early on for both Covid testing, respiratory testing, and then later on strep testing. We have Epic as our EMR and we have Telcor as our point of care middleware database. It became clear right away that we needed to have some sort of Covid ordering guidance, and it wasn't so much necessarily for the providers, but things were changing so rapidly, like who we could test, how much time do we have to test them, which platform did we want to use. I don't know if you remember, but at one point we couldn't get supplies enough for just one platform, so we got supplies in for our Thermo Fisher Amplitude, we got some supplies for Roche, some for Cepheid, and we had to kind of move around what supplies we got which week.

This guidance was huge with that because we could just change based on symptoms. Say if somebody has major symptoms, we're going to let you run a PCR in point of care. If they have minor symptoms, we're going to have you collect and send to the main lab to be run on our Thermo Fisher workhorse that will just have a super high throughput. Over the years, we still use this guidance. It has changed incredibly, because we don't really have to worry so much about inventory management, but the cool thing is, is if we ever did come back into some sort of pandemic or some need to move around supplies or to direct the testing in a certain way, we just change up this guidance for them for the providers in Epic. They would just go down this little list, answer questions; is the person homeless, are they pregnant, are they in the emergency room right now, things like that, and it would guide them to the right test and how to run it.

The other thing that we did recently, we started looking at strep. I have a study going on right now with our pharmacy group. We have pharmacy residents and we designed a study looking at antibiotic stewardship and antibiotic ordering. One of the things we realized is that we had a very old strep ordering algorithm going on in the background, in Epic, that the laboratory didn't know anything about. Along with our head infectious disease provider and our head pathologist, laboratory medical director, we put this modified center score in Epic also for the providers to help guide them toward ordering for strep so that it wasn't just sort of ... In some clinics it was a free for all, in some clinics they just wanted to order culture. In some, they just wanted to order PCR.

One of the other things that we've been looking at and that we recently completed on the hospital acute side, they wanted to remove pharyngitis cultures a hundred percent and just go strictly to PCR. We were wondering at the point of care like, "Ooh. How are we going to do that? How is that going to work? Are we going to align with the labs with this?" We did. What we did, instead of having any clinics use antigen, we removed all antigen testing, replaced it with PCR testing and removed pharyngitis screens a hundred percent at UC Health. This has been going on for about a year now. We still obviously for any kind of persistent sore throats, anything like that, you can order a regular aerobic culture, in the source put throat, but they're going to look at so many more things than just beta hemolytic strep. That has been in process for about a year and it's going incredibly well. I'm really excited to see what our pharmacy partners are going to find out in terms of antibiotic stewardship. Then we'll have another webinar.

Interfacing results. We talked about this a little bit, but in addition to that revenue capture and getting the results in the patient chart, we also wanted to make sure can we view quality control and positivity, remotely? I have 130 clinics and I have three clinic staff. I have a whole nother hospital staff, which is great, but those three clinic staff need to be able to stay on top of quality control, positivity and also, like we mentioned before, contamination. We wanted to be able to remotely view what was going on. Additionally, we wanted to be able to use operator lockout. Why is that important? Because we'd wanted to make sure that the people that were doing the testing had already had the appropriate training. We have online modules, we'll talk about in another slide, but we wanted to make sure they had actually gone through the training and knew what they were doing. We really desired for whatever platform we used to have operator lockout and Cepheid does.

I mentioned our data manager is Telcor. Some of the considerations here that you'd want to look at is how much the driver was. You'd get a quote for that from Telcor, how much the annual support would be on top of that and what other costs would there be to build. I'll tell you right now that my IT resources were amazing. I would not have been able to get through any of Covid without having amazing IT people. I did not build these things, but my IT resources, they took care of all of this. I have to say though, I've been through several large implementations in the laboratory and this was the easiest. I think they had this driver and are reporting out built in probably a week. That's also probably because we had system command breathing down our neck because of Covid, but it was a really, really fast build for our IT partners, which was fantastic.

Partnering with them is very important. We had a project manager initially from IT that helped us organize all of that, all of the considerations for them. We had to make sure that we had enough ports available in each of the clinics. Some of these clinics were really old, so that did take some time too, but I cannot overestimate or over tell you how much IT resources are important in this process.

Training resources. When you have a system as large as mine, you definitely have to think of how are we going to get this training out to everybody? Prior to Covid, we kind of did a face-to-face train the trainer type thing, and we also had new hire orientation in each region, separated out in all three regions. We would gather a hundred new MAs or RNs in a room and do this training face-to-face prior to us doing this standardization.

Of course, during Covid, all of that was gone and this changed the face of point of care even in the hospital setting, because we would do a ton of face-to-face training. Point of care people or staff members across the nation were faced with how do we provide training and how do we do direct observations of testing, especially for non waived testing. How do we do this for our staff? We couldn't do face-to-face anymore, especially ... Then there's also the resources for travel. If you only have three clinic people and 130 clinics, but if online, were there online resources available or is there an option to create online training modules?

Now, Cepheid did have online training modules. We are picky and we made our own training modules online. We use Compass and it's a function in Media Lab. We are able to create our own training modules and we did this for Cepheid and we did it for all of our other platforms. That's really the method we stuck to, even after Covid. We saw no need for waived test systems. We saw no need to do face-to-face anymore, but we still do have key operators that are in each clinic. These key operators, they get the same training as everybody else. Many times we'll have an online chat or an online meeting with them. Now, my clinic members do go out to new locations when we have a new onboarding clinic. They'll go out and train that key operator one-on-one when time allows us to do that.

Specifically for machines, for analyzers, that have a little bit of extra maintenance such as the Cepheid, there'll be monthly maintenance and some quarterly maintenance. We created separate modules for the maintenance and we have the key operators do that. We don't ask that all staff members are trained in this, but I will tell you certainly it's possible to do that, absolutely possible. For us and for our system, we felt like it would be better to train just the key operators in the maintenance portions. Then for the annual service, we have someone from Cepheid come out, a field service engineer come out, and do all of those annual maintenance requirements for us.

I get asked a lot about how we did our verification, especially by laboratorians. When you have a non waived system in the laboratory, doing a verification of a test it can be very burdensome. There's a lot of regulations that you have to follow, a lot of specifications you have to meet. Again, at the beginning it was EUA, but it was EUA waived, and so our direction was to treat it as a waived instrument. For waiveds in Colorado, under CLIA, you have to follow manufacturer's instructions. For this test, the manufacturer's instructions were to run QC on each new machine installed. Because we were where we were at Covid and because we were evaluating all these new methods, our pathologist group did want to do some sort of additional verification of the system as a whole, especially because the Xpresses were new to our system.

What we did is we considered all 30 at the time, all 30 of our clinics as one facility, and we did a verification on one Xpress instrument. We used nine samples, and so we did three positive, three at cutoff, right at the CT value where it went negative, and then three absolutely negative specimens. We ran this on one machine. We got samples from our main lab and they had also been already run on the lab. We wanted to make sure that we had a hundred percent correlation between both the clinical laboratory and the point of care instrument, which we did, of course. Then once we had that information, that was considered our system verification for this testing platform. Any other machine then that we placed, we just ran the quality control on each new machine and that was considered the verification for that machine.

I'm going to talk a little bit about the rollout, how I was actually able to do this. Again, I had a lot of encouragement from my system command to make it happen yesterday, when we were in the middle of Covid, but we did have a lot of pre-work that we had to get done first before we could start rolling them out. I mentioned data ports. Some of these clinics were really old, and so we had an amazing group of facility staff members in each region that went out and evaluated every single clinic and saw, Hey, they've got data ports, we're good to go. Once you have data ports, you have to make them live, so that was an additional step at every clinic.

Once we identified which clinics were going to go first, we sent facilities out. They kind have took care of this on a rolling basis for us, and they basically stayed one step ahead of us throughout the whole process. Because it was Covid, we obviously went with the clinics with the highest volume first and, at the time, some of our clinics were closed. Some of the highest volume clinics were doing drive-through testing at the time, and so we wanted to support those clinics first. Then as clinics started opening, we added them to our list.

The other thing that we had to do is gather employee names and IDs because we decided to be interfaced. On the hospital side, that's a pretty normal thing. We do that all the time for hospital point of care, but for clinics, we didn't have any of the testing interfaced before this. That was kind of a heavy lift getting all these employee names, all of their employee IDs, people transcribed them all the time. We had to get all of that information into Telcor manually. But Telcor does have the ability to take an entire spreadsheet and import those, so I feel like we did a little bit of both at the time. Then, of course, there's the IT work group. We had that driver built and there was a little bit of work they had to do to add the clinics for each wave.

So as far as timing, we basically did four waves for our initial rollout. We would do 10 analyzers or 10 clinics every three weeks. Rinse and repeat. Week one, we would have shipping and installation to all 10 locations. My three team members, and we pulled a little bit from our hospital team as well to help them out on this, but our three team members would go out, install the machine, install the ADF, which is the software that you need. They get it connected to Telcor, connected to Epic, and that comprised week one. Week two was when we all did the training and the testing of the machine. So quality control was run on the machine. We did all of the online modules. Every employee from each clinic had to go through the modules, get signed off and have their name in Telcor. We made it so that they were able to do the testing so they could scan their badge.

Then week three was always a go live on Tuesday, because Tuesday felt like a good day to do that. We had the rest of the week to troubleshoot kind of any issues. That felt, initially, like a really, really fast timeline, but at the end it ended up being a great timeline. Three weeks really worked well. We repeated that a couple of times, and then the fourth wave was right before Christmas honestly, and we had 30 left and I gave my team the option of rolling out 30 all at once or extending this over Christmas. They wanted to do 30 all at once. I will tell you, that seems like a lot, but it actually went really well, especially since we already had done what, 10, 20 ... We'd already done 30 machines. We rolled out the last 30 initially before Christmas and then we kept going after Christmas.

I've mentioned the C360 software before, but this is the software that can be installed with the Cepheid machines. Initially, I didn't really think I was going to use it that much. I knew that we could monitor positivity, I knew that we could see the machines remotely, but I didn't really know how to use it or how it would benefit me. Turns out we use it quite a bit. Now we can see which machines are giving positives. We can make sure that we're not seeing any contamination like module one at Aspen Creek Clinic is almost a hundred percent positive. We've never had that happen, so I'm imagining what would happen. We can monitor that now and we can actually pull graphs of positivity and make sure we don't have one machine that's acting up over any of the others.

The other thing we began doing is a pilot with tech support. Because we were such a large system, sometimes when we call into tech support with a module issue, I would ask them, "Are we seeing the same module issue across the board?" Well, they didn't really know what to say because at that point they weren't treating us as a system. That one tech support person we were talking to didn't realize that we had 80 more machines out there. Tech support began a pilot with us where they actually started monitoring us and monitoring our analyzers as a system, and then they would contact us if they saw a module failing and we would have an FSE out to our site almost before we even knew anything was wrong. That has been a fantastic pilot and something that we continue doing down to this day that has been just a really ... It's been a huge win for us.

The other thing that we didn't have before Covid, we had been doing flu and RSV testing, antigen. We'd been doing antigen testing. Again, we weren't interfaced, so not all of the results were going into the chart. If they were going into the chart, it was under provider notes. It wasn't falling under the lab results tab in Epic where it had a reference range or where it could be tracked easily. They were just falling under provider notes. Historically, in the hospital setting, everybody in microbiology always waits for the first hospitalized flu of the season, and that somehow signifies that the flu season has begun. Now, however, because I have everything interfaced, I can watch flu and RSV, I can watch the uptick and then provide that information to our hospital labs and say, "Guys, it's coming. I'm seeing a lot of flu As," or, "I'm seeing a lot of flu Bs," or you know, "Our RSV is really spiking, especially in the northern region." I can give them so much more data than we ever had before. We did not have this surveillance before and it's amazing.

Lastly, inventory management. As soon as I see that uptick, I can contact the clinics and say, "Hey ..." Because they see it every day and they feel that things are increasing, but they don't know how much everything is increasing. I'm actually able to say, "Hey. You've done 20% more in the last two weeks than you have all the rest of the summer. Now is the time to start ordering and getting your supply in ahead of time."

Some of our outcomes. As far as, again, like I mentioned, the antibiotic stewardship, we're still gathering hard data, but anecdotally, providers are more confident in the result and they don't prescribe antibiotics for a negative result like they used to with the rapid antigen. Do we look at that? We do. I still pull results. Initially, I still had some locations that still had some stockpiled antigen tests and they would use those. They also were using the antigen test for some off-label testing that we found out about, but this is a really good thing. If you ask any point of care person, anytime you go into a clinic, you always find surprising things when you go in.

We found some surprising uses and some off-label uses that we've been able to sort of curb now, and we still, every once in a while, see a provider order a culture on a negative PCR result. But again, some of these are for patients they'll have persistent sore throats, and so that's the reason for ordering the culture. It's been fantastic to be able to see all that information. I really hope that when our pharmacy partners finish with this study, we'll be able to have some more concrete data as far as has our antibiotic stewardship increased, have we been doing better.

Staff appreciation. I'll tell you, during Covid, I had to bring my daughter in for a UTI to one of the urgent caress. When I came in, I sort of slunked like, oh gosh, they were so busy with Covid and I felt bad, but I kind of snuck past the lab and I peeked in and they were doing all their testing. I was like, "Oh, they probably hate me." When I went in there, I was hoping no one recognized me, and of course they did. They said, "Thank you so much for giving us a machine." And I said, "What?" They're like, "Our patients ask for this. They know the difference between PCR and antigen. They want this testing. They're happy that we have it and they're happy we can do it right here and not have it sent off and have to wait. We can give them a result right here." I felt so relieved. I thought I was going to get killed by the nurses that had to do this testing, and instead they loved it and they were grateful for it. So I felt so much better.

As I mentioned before, staff ease of use, they find it much easier than the previous methods. We had several methods going on, of course, but once you get a flow going, they totally felt like the whole flow overall was easier, especially since it was interfaced and the results went straight to the patient app. It made everything, all the bookkeeping on the backend, so much easier for them.

The other thing we found is that, in some of the busier clinics, we did have to put a lab or a tube rack because they would have them backed up. Now in some of our urgent cares, we actually do have two machines. In our top five busiest urgent cares they have two machines and use them a hundred percent. They've got room to do eight tests all at once. Honestly, in our primary cares, most of the primary cares have what's called a two bay. They've got the two modules. Some of the busier ones have four. All of the urgent cares have four bays, but again, the top five, maybe seven now, all have two four bays that they run side by side pretty much all the time.

Our system command was very pleased, at the beginning of Covid, that we were able to roll out the testing in our non-acute sites, the same testing that the patients would receive in the laboratory. We have gotten such amazing patient feedback from that. They felt great that they could get that test and not have the provider say, "Well, this is just point of care. Let's send it to lab to be sure." Nobody wants to hear that anymore. They want the right test, right away. We have been so pleased that we've been able to offer that to our patients across the board.

My team, again, surprisingly, we didn't think we were going to use C360. We did love the ability to be able to monitor device errors and positivity using this software, especially since all of us, I think half of us we began our career in mirobiology. It was a leap of faith to give point of care to non laboratorians and just hope that it works. It's been amazing. It's been really cool to bring that side of our career into point of care, something we never thought was going to intertwine before. Then, again, lastly, we've had real-time flu and RSV surveillance in the community that we didn't have. This has been able to help us with inventory management, especially with flu season coming up, and also give our pathologists and infectious disease partners a heads-up when we start seeing increases in these viruses in our community especially. And strep too. We've been watching strep go up and down, although strep doesn't go down as much as it used to. It's almost like a year round thing now.

Daniel Williams:

All right. Mary, that was a wonderful presentation. Thank you so much for all that great information. I wanted to remind everyone, if you look at the bottom of your screen, you'll see that Q&A is one of the options. Just click on that item there and drop in any questions you have for Mary. We do have several that have already come in. Mary, let's start getting to those. We've got about 10 or so minutes that we can field those Q&A questions.

First one is, we've got a lot here about the equipment itself, so how many ports does an instrument require?

Mary Hammel:

That's a great question. It just requires one. You'll need a plug and a port. We didn't have any problem with this, but I can also imagine that some clinics might. The height of it, it's not incredibly tall, but you would have to make sure that you've got room if you've got cabinets above. I'm thinking about all of our clinics, they have usually one little strip of counter space that they get for their "lab", and so there's always cabinets above it. You'd want to make sure that that space was also adequate. Yeah. One port, one plug and that's it.

Daniel Williams:

That's great. Okay. Thanks for sharing that. Next question that's come in, who is able to access C360 data and follow up here is the information real-time information?

Mary Hammel:

It is real time information. Yeah. As far as who's able to access it, I set up access for my entire team. You could set up access, in theory, for a clinic manager easily, really anybody that you want to have that information. The way my system is set up, I really want nurses and MAs to be able to do patient care. One of the things that I've always designed our program to be is so that my clinic staff, my clinical laboratory staff, take care of those things for the managers and communicate out to the managers. I currently don't have any of the clinic managers have access to C360, but it's not because they couldn't, they absolutely could if you had a clinic that was kind of running on its own, didn't necessarily have the same type of laboratory support, maybe didn't need that laboratory support, they could absolutely have that access. It is real time.

Daniel Williams:

Okay. Let's see, next question that's come in. Is the strep test used on every strep suspected patient. How do you kind of discern who gets tested and who doesn't?

Mary Hammel:

Good question. If there's going to be a strep test done, yes, it is done PCR. We don't have an option to run antigen for certain symptoms or a PCR for certain symptoms. It is a hundred percent PCR, both in the outpatient space and on the acute hospital space. What we did find out when we went ... We went through recently a strep supply back order., When we were looking at our use, especially some clinics would be super high on their use all the time, a hundred percent year round, and some of our clinics wouldn't have any testing and they would send it all out to the lab. We started looking at the algorithms behind that testing and realized there was some really old, outdated strep algorithms that we didn't even know existed.

Our head infectious disease doc and our head pathologist started working up on that modified center score that pops up. When a provider clicks on strep, that center score will come up and remind them and kind of give them a real quick visual and it says, "Is your score greater than two, yes or no?" It's not a hard stop. The provider can still order it, if they want, it's simply a guidance. So that's how we were able to move through that. It was really funny when the funny things you find when the need is there, and we had this algorithm that was completely outdated that nobody even knew existed. It was really good to nail that down and get it a little bit more practical and up to date.

Daniel Williams:

Okay. Thank you. That's very helpful. Another one, I love this, how large is this system? It looks like it takes up a lot of space. I mean, do we have the right dimensions here? Give us an idea of that so our attendees can get an idea themselves about that.

Mary Hammel:

I should really have an idea of how big it is, but it's no bigger than any ... If you've got a CDC machine, it's smaller than a CDC machine. I would say that it's less than a foot wide and less than a foot tall.

Daniel Williams:

Okay. That is really helpful then.

Mary Hammel:

It's not huge.

Daniel Williams:

Are there any best practices in where to store it, where to keep it then? I mean it obviously is not taking up a lot of space, but where do you guys keep the machine?

Mary Hammel:

Well, as with any laboratory that you set up, you're going to want to make sure that that is away from your nurses' station and away from food or drink. In a typical setup in primary care, for example, you'll have your urinalysis machine, you'll have the Cepheid and you'll have any other kit tests on that space there, maybe [inaudible 00:51:23] we do the hemoglobin A1C. You'll have all of those next to each other and it doesn't take up a ton of space. As far as space consideration, you'll want to make sure you've got enough light. You'll want to make sure that you have, and I see Keil put in the dimension [inaudible 00:51:39]. Thanks, Keil.

Daniel Williams:

That is really helpful. Yeah.

Mary Hammel:

You'll want to make sure that you don't have it next to food or drink, but that's with any laboratory testing, right?

Daniel Williams:

Sure. Okay. Thank you, Keil. If you look in the chat area, we've got the actual dimensions written down there, so that is really helpful as well. Here's another one that's come in. I did want to say, before I read this one off, one more chance here if anybody does want to drop an additional Q&A question. This is the last one that's come in so far. Just let us know there.

What pushback, if any, did you receive from providers?

Mary Hammel:

I think the larger pushback was probably from strep because the dipstick is easy, the antigen test is easy to do. It's fast, it was five minutes to do that. Again, we also had other platforms, but by far it was the antigen test that was being done in most of the locations. It's not to say they didn't know about PCR, but truly the nitty-gritty about PCR they didn't know about PCR, they knew what it was called and they knew that it was good. When you started talking about the fact that with that antigen test, and I would script this to them, with that antigen test, what they're doing is they're saying to the patient, "Well, hey, it's negative, but there's a 20% chance that it might be not negative. What we're going to do is we're going to send it for a culture or we're going to just give you antibiotics, because you look like you have strep." When I would say that to the providers, they're like, "Yeah. That's what we do."

And then I would tell them, "Hey, with the PCR though, you can run this test. You can have confidence a hundred percent that that target that we were looking for in the PCR was amplified, amplified, amplified, and it was not found. You can have confidence that this person does not have strep." The pushback really quickly declined, honestly.

In the pediatric clinics, there was still some ask because they were using it off-label and we had to address that on the side. As far as pushback for Covid, I think the providers were just happy to have that testing. Of course, in some clinics there was a lot ... In some of the bigger clinics, there was a ton of demand, so a lot of what we had to do was move our patients ... We turned on self-scheduling so patients could schedule and go to different clinics and we could turn off certain clinics so that we wouldn't be overburdening them, but by and large, they were happy to have the test. We just had to direct where people were going for the testing.

Daniel Williams:

Yeah. Mary, you have made a lot of great points today, covered a lot of material. What's a final thought then for anybody who's wanting to adopt this, either a best practice, a first next step, anything like that that you want to share, as a final thought.

Mary Hammel:

From a laboratorian standpoint, it does feel scary to provide PCR testing to nursing staff, it's not. It went so much better than you could have imagined. Really look into the technology and embrace it and it's not scary. From a provider standpoint, I know it seems like having a longer test could keep patients in the clinic longer, and I know that there are reimbursement concerns, work with your billing analysts because they should be able to really ... We haven't had any issues with that. Really look at the testing, look at how long your patient's already staying in clinic and kind of say, well, if I had a five-minute test, would they have actually gotten out any faster compared to a little over a 20-minute test? Would they have gotten out any faster? I bet you the answer's no.

Daniel Williams:

Okay. Thank you for sharing that. Again, great presentation. Thanks everybody for participating in today's program. The education for this session has now ended. Once again, we'd like to thank Cepheid for their sponsorship today. Please visit their website at cepheid.com/mgma where you can learn how their game-changing RT PCR platform can help your organization increase practice efficiencies, patient satisfaction, and revenues.

Now, if you do have content questions, you can direct those to Keil Brinster at keil.brister@cepheid.com. You can see it on the slide as well. If you do have a webinar question, contact ed@mgma.com. If you haven't already, please be sure to click on the evaluation link. It's located in the learning management system. After completing that evaluation, which is required to claim credit, please allow 24 hours for system communications to process credit for this session. For information on all of our conferences and webinars, please see the MGMA events page. Thank you everyone, and see you at another online event soon.

Speaker 1:

Welcome to this podcast, brought to you by the Journal of Healthcare Contracting, and now our host, Publisher John Pritchard.

John Pritchard:

Hey, guys. This is John Pritchard with the Journal of Healthcare Contracting. I'm excited today to have Dave Persing on the line with me. Dave's the Chief Medical and Technology officer at Cepheid, and he and I talked a little bit about how the rapid testing world has evolved and become imperative for health systems to be great at testing. Dave, thanks for being with us today. Let's jump right in. How has PCR rapid testing changed because of the pandemic and how did we get to where we are today?

Dave Persing:

It's really interesting to see the evolution of molecular diagnostics over the past few decades that I've been involved with it. I like to say that it's now known, at the public level, the difference between PCR and CPR. They actually know the difference now. PCR has been the cornerstone of molecular diagnostics for many years, but it really hasn't hit the headlines until COVID hit, and that's really for good reason because it's more sensitive and that can be viewed as good or bad depending on the circumstances. But in the setting of sick patients coming into the hospital, you really do want the most sensitive test. You don't want a test that's going to miss a case that's admitted to the hospital, not in respiratory isolation, so the regular ward, and then to later find out a day later that they're COVID positive, that's not a good thing. Having a really sensitive test upfront on admission is really important. That's the role that PCR plays these days in COVID and really has been driven in that direction because of the pandemic. I will say that prior to COVID, seasonal influenza was our biggest challenge. The same idea applies there, that there are less sensitive tests that can be used to diagnose influenza, but in the hospital setting, you really want the most sensitive tests because you don't want to be surprised. You want to know whether the patient is eligible for an antiviral, whether they need isolation or not, and how they are managed after admission is very much dependent on getting an accurate result. That's often driven by molecular methods like PCR.

John Pritchard:

That's very interesting. You touched on something there I'd like to dive a little deeper into. Why is it so important to get rapid testing accurate?

Dave Persing:

Well, there's an old saying that a company may say, "We have rapid and we have accurate. Which one do you prefer, rapid or accurate? Not both." But now, having the combination of accuracy and speed is something that these methods offer that really didn't exist before. That's the difference, is that in the past, you always had to make sacrifices in sensitivity and performance in exchange for speed. Even with that drop in sensitivity, sometimes the decision was made in favor of time to result because the results are more actionable. Clinical action can be taken more quickly, whereas waiting for an ultra sensitive test based on PCR that had to be sent through a lab and got back two days later was just not actionable, from a medical management standpoint. Now having this combination of the best in class laboratory quality accuracy along with speed is really a unique combination.

John Pritchard:

What are the three to five things a supply chain leader really needs to understand when evaluating testing platforms?

Dave Persing:

Well, obviously, test availability is one of them, and I think the entire world saw a major manufacturing squeeze and constraints on supply during COVID. Cepheid was among them, but we were flanked by many of our competitors that had similar supply constraints. It's not just the tests though, it's the stuff that goes into the tests. It's the swabs, it's the transport media, all of which experienced supply constraints during COVID. Looking at the entire workflow, from sample collection to testing, is important to get a perspective on from a supply chain perspective. Obviously, tests that contain all those materials with the test kit, the transport medium, and the swabs together as a single package on a per patient basis is important because that means that you won't have situations where you have tests but no swabs, or swabs but no tests. You're going to have them linked together. One of the other things that I think is going to be important is to consider the versatility of the platform that is being used in hospitals, is how does that platform go back and forth between seasonal presentations of viral infections versus out of season uses of that technology? How does it go back and forth between the current pandemic and, God forbid, the next pandemic? How do those systems stay in use during that period of time? Because ideally, if we have to respond to the next pandemic, it needs to be on the basis of a system that's already in the hospitals, that's already in use, that so-called warm testing capacity that's used for so-called peace time wartime scenarios where you use it for routine testing for chlamydia, gonorrhea, viral load, healthcare-associated infection, C. difficile, those kinds of applications in between pandemics. We saw during the pandemic, where there was a demand shift away from healthcare associated infections and tuberculosis testing toward COVID testing, we saw a reduction in chlamydia and gonorrhea testing because of COVID. Part of that was because patients weren't showing up in clinics, but also there was just a natural demand shift toward the pandemic response. But it's all predicated on having a system that can do it all, that can respond to a pandemic but also can be used for other applications outside of pandemics. Having the personnel trained and onsite, having a system that's easy to use that can run tests on demand is an important part of that formula.

John Pritchard:

Very interesting. I'm going to ask you now to look a little bit into your crystal ball. Looking to the future, what is Cepheid doing to prepare for the next pandemic-like crisis in the healthcare industry?

Dave Persing:

Yeah, that's a really good question. Cepheid has a long track record of responding to emergency threats. We were engaged early on after the anthrax scare in 2001 to build a test cartridge that could test the mail for the presence of anthrax. We were early in responding to the threat of drug-resistant tuberculosis. Starting in 2005, we started a project that would target drug-resistant TB. In 2009, we built a test for H1N1 influenza. In 2014, we built a test for Ebola. More recently, we responded very quickly to the threat of COVID. But we feel that it's really important to the tests that we design to build in a future-proofed capability that enables us to be able to detect things that may not yet be on our radar. For instance, our influenza test for influenza A, B, which also includes respiratory syncytial virus and COVID, the so-called 4-Plex test already has built into it capability of broad range detection of influenza A virus. Influenza A virus is a category of influenza virus that includes avian influenza. All the bird flu scares you hear about have not amounted to an avian flu pandemic, but because the virus is out there, the potential exists for it to cross over into the human population. We need to have tests that are ready to detect it that are already in routine use. Every time you run a Cepheid test for flu A, flu B, RSV, and COVID, you're actually running a test that covers many influenza A viruses, including avian flu viruses. That enables you to be able to detect it in circumstances where other tests, especially immunoassay tests, will just miss it. We learned our lesson after 2009 H1N1 when many of the antigen tests that were out there for flu lost most of their sensitivity. The CDC reported that test sensitivity went down as low as 11% and was hit hard by the change in the antigenic structure of the flu during that season because the lateral flow tests that were in use didn't have antibodies that could recognize that particular strain of virus. By building in this broad range capability into nucleic acid tests, we can avoid that problem of missing variants that exist out there, including influenza variants and COVID variants that may appear in the future.

John Pritchard:

Dave, this has been a great conversation. Thanks so much for sharing your insights with us. Listeners, I want to take a quick second to thank Cepheid for sponsoring this podcast. We wouldn't be able to bring you guys such relevant, timely content without partners like Cepheid. Always, thanks for tuning in.

Speaker: Bryan Turner:

Hello, everyone, and thank you for attending today's webinar: Rapid Molecular Diagnostics for Sexual and Women's Health. I'm Bryan Turner, a marketing manager for Cepheid, and I'll be introducing our speaker, Amery Vilander. Amery serves as the microbiology lab manager for UC Health Memorial Hospital in Colorado Springs. She participates on several teams within UC Health, including the microbiology molecular best practices team, the South Region Antimicrobial Stewardship Work Group, and the Infection Prevention Work Group. Amery has extensive experience with all facets of new molecular test implementation in a hospital laboratory, from conducting the verification process, insuring CAP compliance, to keeping microbiology lab staff engaged. In 2021, Amery earned the Clinical Excellence Award for transformation leadership from UC Health Memorial Central. She welcomes the opportunity to share with others her experiences in onboarding new tests and best practices she has implemented at UC Health, and now I will hand it over to our speaker.

Speaker: Amery Vilander:

Okay, so the objectives for today, first we're going to discuss the most recent CDC surveillance data for sexually transmitted infections. I'll also explain the benefits of rapid, on-demand molecular diagnostics compared to traditional methods like culturing, and wet preps, and of course batch testing. We'll become familiar with common molecular testing options for group B strep, chlamydia trachomatis, neisseria gonorrhoeae, and vaginitis. And then lastly, we'll talk about some key considerations that you'll want to think about when you're implementing a new molecular diagnostic assay in your laboratory. Today's disclosures. I do have an honorarium for this presentation provided by the Cepheid Speakers Bureau, and a couple of abbreviations there. Really long names for organisms, so I'm going to use CT for chlamydia trachomatis and NG for neisseria gonorrhoeae. I may also call it GC as well, for gonococcus.

The CDC surveillance data, in 2021, this was preliminary data. CDC says 2.5 million reported cases of chlamydia, gonorrhea, and syphilis. Now, if you do the sexually transmitted disease testing in your laboratory, you may have noticed over the last several years, an increase in positivity for your tests. It is something that we noticed over the last few years, and CDC's last report was published in 2020. It is something that they report on every year, and in 2021, they have released some preliminary data. Something to consider for surveillance data is that this report for 2021 is going to be finalized probably later this year, and the '21 report ran data through the fall of 2022.

So the impact of COVID on sexually transmitted infections, you may be wondering what happened during this time. Even though we've been seeing kind of the steady march of increase in infections over the last few years, we would theorize that maybe something declined a little bit during COVID. In actuality, case counts in 2020 were all higher than 2019. Now, they did fall in the early days of the pandemic, in March and April. So you'll see here that, for gonorrhea and syphilis, it was a very steady, and sometimes a very steep increase, in case detection, but you'll notice, for chlamydia, kind of that sharp drop there, and what CDC is saying to explain that drop in chlamydia was kind of multifactorial.

There were reduced preventative screenings during that time. The shift in resources to COVID, and really looking at symptomatic patients, and something about chlamydia is that oftentimes, patients are asymptomatic, so the detection of the positive cases is really done through a routine preventative screening. Obviously, social distancing was also limiting sexual activity, so overall, with these reasons, CDC says that that is why chlamydia was disproportionately affected, compared to GC and syphilis. And chlamydia actually had a 13% drop by the end of 2020, so again with that sharp decline. But you can tell by 2021, things were starting to rise as the communities started to reopen.

For drug resistant gonorrhea, or GC, there is a CDC report. It's called the AR Threats Report. It was last published in 2019, and there are actually three categories, organisms, for this report, primarily bacteria and yeast. The first category is concerning, second category is serious, and then the top category is urgent. And you'll notice that the CDC has actually put drug-resistant neisseria gonorrhoeae, or GC, into that top category for concern. 550,000 drug-resistant infections every year, 1.14 million total new infections each year, and several hundred million in terms of lifetime direct medical costs. On the right here, we have this graph that shows emerging antibiotic resistance over the last 16 years, and kind of the timeline for how treatment has evolved over time. Currently, ceftriaxone is the recommended drug of treatment.

For pharyngeal infections, the CDC does have STI treatment guidelines. They were updated in 2021. The last time they were updated was 2015. And something about pharyngeal gonorrhea is that it's largely asymptomatic, and it is common in certain patient populations. It is harder to eradicate compared to urogenital or rectal, so this is something that maybe not a lot of people know about, when you have gonorrhea in the pharyngeal area, that you actually want to have a tested cure seven to 14 days after initial treatment, and again, three months anywhere up to 12 months afterward.

NAT, nucleic acid amplification testing, is superior to culture in that regard, and then CDC says, in these STI treatment guidelines, that you do not need to retest if your infection is in the urogenital or rectal area, but pharyngeal, you need to treat and then test for cure, because it's hard to eradicate. So when you have a suspected treatment failure, you should have both NAT testing and culture, and then if you grow it upon culture, you should do susceptibility testing. And I realize not a lot of labs out there will do automatic AST testing on a neisseria gonorrhoeae isolate, so that's something you'll want to send to your reference lab if there is a request for that.

Now, with pharyngeal infections of gonorrhea, not all assays have that as a specimen type in their assay, so you will want to read the instructions for use, or the package insert more commonly called. Sensitivity and specificity are going to vary for pharyngeal, potentially, versus urogenital or rectal. And then some assays do have cross-reactivity with your commensal or like your normal flora neisseria, species that are in the pharynx. These are things to consider when we are talking about pharyngeal infections for gonorrhea.

The CDC surveillance data for group B strep and vaginitis. I'll talk about group B strep first. The CDC does have an Emerging Infections Program, and this is a program that encompasses multiple states across the country. You may be in a state that participates in this. I know Colorado is one of them. In 2020, they reported on the national estimates of invasive disease, and what we define as invasive disease is when group B strep is found in a sterile body site, such as blood or spinal fluid.

So you can see early-onset cases there, late-onset cases, total cases, and deaths. This is a pathogen that is very capable of causing serious harm, and the references there at the bottom, it's a wonderful report if you would like to take a look at it. It actually atomizes by state if you'd like to take a look at that. This is why it's important and in CDC guidelines to test for group B strep.

For vaginitis, we're really talking about bacterial vaginosis, candidiasis, and trichomoniasis. The CDC has national estimates of disease, and the statistics are pulled right off the CDC website, with the references listed below for you there. Bacterial vaginosis is the most common vaginal condition in women between the ages of 14 to 49, 29.2%. Candidiasis is the second most common vaginal condition, with an estimated 1.4 million outpatient visits every year. And trichomoniasis, 2.6 million women, 2.1%, ages 14 to 49. For trichomoniasis, it is caused by a parasite, and it is largely asymptomatic, 70% of the time. Women are more likely to have symptoms than men.

All right, next we will talk about rapid diagnostics versus batch testing and traditional methods. The considerations for, if you want to bring up a rapid molecular test versus something else or maybe sticking with your method that might be more traditional, like culturing or wet prep. It's not always an easy decision. Sometimes, it's something that you're asked to do from maybe your medical director, or maybe your customers there in your hospital, or your community. I kind of put together a slide here, of things to think about, right? If you were going to think about doing rapid molecular diagnostics, obviously the benefits are turnaround time. It is going to be faster than waiting for an organism to grow. You are going to have better sensitivity, meaning you're going to pick up, potentially, small numbers of organisms that maybe you don't even get to grow on culture.

And then, consider that molecular diagnostics, especially in the setting of CT and NG in emergency departments, if they have the result, it helps to avoid over- or under-treatment. So there's a great study there I've listed at the bottom, of a randomized clinical trial, where they looked at CT/NG in an emergency department for women, and what they realized was that if they had patients that had the rapid diagnostic done, they have the right treatment, and correct meaning correct to that result, right? If they didn't have it, they would either be under-treated or over-treated, so I think that's a really great study to look at if you're kind of trying to figure out, "Do we implement CT/NG in the emergency department, for emergency department patients? Do we batch it? Maybe we run it 24/7."

The other things to consider for rapid molecular diagnostics are what are your test volumes expected to be, and your instrumentation, and your staffing. Obviously, that's important to make sure that you have the infrastructure to be able to accommodate a rapid test volume, especially if it's significant. You'll want to think about what kind of resources you have for doing a verification study, and implementing that, and really managing that project. There are supply and labor costs to consider, and you'll want to get input from your stakeholders. These are the people who are involved, not only with running the tests, but also who order the tests. This might be looking at who is it that would potentially order this test? It could be your emergency department. It could be your women's clinics, or your OB/Gyn, possibly your primary care clinics and urgent cares, so those are things that you'll want to consider and get buy-in from them, and let them know that this might be an assay that could be of value.

And then if you're part of a system, you know, a larger health system, and you have some guidelines in place to standardize practices, or maybe you have an existing agreement with a current instrument platform, these are all going to roll into your decision of timing, and when we switch, or do we switch? And of course, test complexity and personnel requirements. A lot of molecular testing is moderate complexity, but some of it is high complexity, so you'll want to consider what kind of personnel you have and the requirements for your assay.

[inaudible 00:15:09] right? Let's talk about, maybe I decide not to do rapid molecular. Okay, so maybe I decide, "Do I want to stay in culturing? Do I want to stay on wet preps?" Like I mentioned in the setting of vaginitis. Maybe we want to batch our assays. Obviously, there are some benefits to doing that. Your supply costs are typically way less, and you may have some fewer regulatory requirements if we're talking about sticking with cultures and wet preps, in terms of you wouldn't need to do a verification study.

But some things to consider for a traditional method is that if you're going to go with culture, even it's in the setting of group B strep, or chlamydia, or GC, some of these organisms take several days to grow, organism identification does require high-complexity testing for personnel, and your cultures are going to incur additional charges for organism ID. And then in the setting of chlamydia, not only does it take a long time to grow, you need special media in order to do that. So largely, for CT/NG, and also for some of your vaginitis targets, this is where maybe molecular may come in and be a better choice for you. And for BV, bacterial vaginosis, Gardnerella vaginalis and lactobacillus are actually not specific, due to being found in healthy women. There is a study there by Fredricks, that talks about how Gardnerella vaginalis can be found in up to 70% of healthy women, and I will say that when we get to a later part of the presentation, it is something that we kind of noticed in our previous assay about, "Wow, why are we seeing so much Gardnerella?" That started the wheels turning in our head initially, but it started with that.

Group B strep, non-beta-hemolytic strep B, can be missed on culture, so I believe it's about 20% of group B strep can actually be non-hemolytic, so that means if you're screening for your cultures and you're looking just for beta-hemolysis, there is a possibility that you would miss group B strep on there, especially if there's a lot of vaginal flora growing on that plate. And of course, for trichomoniasis, on a wet prep, you need to visualize the movement, that kind of jerky movement, in order to be able to report the trichomoniasis. Typically, it's about a one-hour time before they start to die. So, considering, "Do we go rapid molecular? Do we stay with our current method?" These are things to consider.

All right, so rapid molecular diagnostics. We'll be talking about GBS, group B strep, CT/NG, and vaginitis. We'll start with the group B strep rapid platforms. These are kind of the most common platforms. There may be others out there on the market. You know, these are the ones that are the most common, the Hologic Panther Fusion, Luminex Aries, Cepheid GeneXpert, and the BD Max. They will vary from being a floor-standing model to bench top model, roughly equivalent sensitivity and specificity among the models. For Cepheid GeneXpert, they do have a way to do two different assays, so I will say for all four of these methods here on the screen, they are all done on enriched vaginal-rectal swabs, in Lim Broth typically, and that is the method of detection that the CDC and ASM recommend for group B strep. As a matter of fact, there are catch-up list questions related to that.

Now, for the Cepheid assay, it is the only one that does have an option to do a direct method off of your vaginal-rectal swab, and that is typically for women in intrapartum settings, so they're already in labor and delivery. And that is a different assay, it's called the GBS assay, than the enriched assays. The enriched assay is GBS, LB, XC. It's typically for prenatal settings, and done on an enriched Lim Broth.

So there's actually a really good study out of UC San Diego there, from Dr. David Pride. He compares several methods for group B strep detection, molecular, and this quote is from an article. And really, it talks about how group B strep should be detected by NAT testing as the gold standard. Less hands-on time, definitely. You can throughput a lot of samples, especially if you have a patient population that sends a lot of GBS testing to you, faster time to result, and greater sensitivity. You're not going to miss some of the most hard-to-find GBSs that might be buried in the plate with other vaginal flora.

Next, I'll talk about CT/NG rapid platforms. Three most common assays out there on the market, Hologic Panther, the BD Max, and the Cepheid GeneXpert. Now, there are a variety of specimen times. Genital and urine tend to be done on all three. Now, extragenital sites may not be done on all of them. You are going to want to look at your IFUs, your package inserts. Sensitivity and specificity is going to vary by the organism, so you may have a different one, different sensitivity and specificity for CT versus NG. And then, just wanted to call out that Hologic and Cepheid have a CT/NG assay. The BD Max assay actually is a combo, and includes trich, so it's CT, NG, and trichomoniasis. Now, for all three of these, they are FDA cleared for vaginal self-collection in a clinical setting, or clinician collection.

So you may be wondering why is there a thing about vaginal-self collection? As explained to me by our ED partners, this is something I've learned more recently. It's not something that we really think about in the laboratory, right? You think, "Oh, the clinician collects the specimen," but for some patients who may have a history of sexual trauma, or they just would prefer to not have a clinician do a pelvic exam on them, the option to do a self-collection really is just such a welcome relief for some patients. So the sensitivity and specificity numbers that are there, those are for female urines, and then endocervical swab, so you can see that all of them have about 90% sensitivity, specificity for both targets.

For vaginitis, we've got four platforms here listed, again, the most common ones. There are some that have just one assay, meaning you're going to detect multiple targets in the one assay, and then for the Hologic Panther, they do separate out their assays, so you'll have to have a separate assay for bacterial vaginosis, and then a separate assay for candida and trichomoniasis. You'll notice on here, for the assays that do have Gardnerella and lacto, they're there in red, as I've mentioned, Gardnerella and lacto can be found in a large percentage of healthy women.

I will mention that the BD Affirm is not cleared for patient self-collection. The other three are, so you know, when we're talking about patients who have a history of sexual trauma, and they are needing and wanting to have a self-collection method, that kind of puts the ED in a difficult position to... if you're running an assay that's not cleared for patient self-collection. And then of course, for a pelvic exam in the emergency department, it often requires two providers in the room, so usually a provider and a second person to assist, so there's a benefit to the ED also, in terms of having self-collection available.

So you'll see, in terms of sensitivity and specificity, again, it's going to vary by organism. And we're talking about bacterial vaginosis, we're talking about yeast, and we're talking about some assays having Gardnerella, or even, when we were talking about a shift into anaerobic environments, we're talking about atopobium, megasphaera, BVAB-2, and that is its name, the name of the organism is BVAB-2. For those of you thinking, "Well, if it's an anaerobe, I should be able to culture it, right?" And these are not organisms that we typically culture. The vaginal specimens, not one that we typically do an anaerobic culture on. Notice that the Cepheid GeneXpert, their MVP assay does not actually detect Gardnerella or lactobacillus, and sensitivity and specificity listed there, on this slide, sensitivity and specificity are over 90% for the Cepheid assay.

Now I'm going to talk about the implementation of the Cepheid MVP assay in our laboratory. As I mentioned, I'm in Colorado. We are in Colorado Springs, which is the Southern region of UC Health, and in the fall, we moved to the MVP assay from our old method, which was the BD Affirm, and the story with MVP kind of began for us in about the early part of 2022. We were having issues with our current assay, and when I found out Cepheid was working on a vaginal assay, and I said, "You know, I think I need to explore this, because I know the hands-on time is really less than what we're currently doing, and it's a method that we're familiar with," and I knew that I needed to pull in the stakeholders to have that discussion.

So Memorial Hospital Central, we are a part of UC Health. I am sitting in that building that you see right there on the lower-left. We are in Colorado Springs. We are a award-winning level one trauma center, with a comprehensive stroke center. My microbiology lab team is comprised of 19 medical laboratory scientists, covering day and evening shifts. We do culture and molecular testing for four hospitals in the [inaudible 00:27:05] UC Health, and we knew that we wanted to switch methods, and this actually began pre-COVID, that we started investigating this.

So why change methods? When we realized that Cepheid was bringing up a new vaginal panel assay, we took a hard look at it and compared it to our current method, and our current method at the time, we were unable to run stats. We had to batch specimens, and we did not have random access, meaning I have a sample, I put it on the analyzer. I have another sample. I put it on the analyzer, to get it running. We did not have the capability to do that. The Affirm required us to do batching. It was a very labor-intensive test. It had many steps, different reagents you had to incubate in certain temperatures, and if you've ever run the BD Affirm assay, you have to squeeze the reagent ampules pretty hard, and talking about motor skills and having to really just squeeze, when you run so many of these samples through in 24 hours, that can present a challenge with ergonomics.

And then also, with the BD Affirm, there was subjective color interpretation. We had to look for rim dots, so then you're going, "Is it blue? Is it light blue? Is it sort of blue?" And this was not a test that we could interface. It was a test that required manual result entry, and then as I mentioned before, it was not FDA cleared for patient self-collection, so that really presented a challenge for our ED partners. So those were our challenges.

So when we moved to the MVP, kind of high-level overview with our wins. We reduced our turnaround time by 21%, and we have a Cepheid GeneXpert Infinity, but even with the Cepheid GeneXpert, you don't need to batch it. It is random access. We were able to interface it to our LIS, which is Epic Beaker, and we were able to set up auto-verification. Now, this is not something you currently do in your microbiology lab. I understand like the concept of it can be scary. I will say that just peruse it, pursue it. Like, ask your LIS partners, ask your chemistry hematology partners. Lots involved in that, because that has really changed how quickly that we can chart results to clinicians for patients.

And obviously, MVP has patient self-collection in a clinical setting, and I can't tell you how eager my staff were to participate in this. They were so motivated. They were wanting to run verification samples. They wanted to bring up this assay. And of course, we pulled in our ED partners, and said, "This is the assay. These are the targets that are going to report. You know, is this something that we can potentially move to?" And it was very warmly embraced.

So I'm going to talk about test implementation, some of the key points that you want to consider. Number one is to identify your stakeholders, and I can't stress this enough. It is going to be for your current tests, you should be able to figure out a way, either running a report or looking at your previously tested patients. Who is ordering your tests? Where are these specimens coming from? And since we're talking about women's and sexual health, group B strep, CT/NG, vaginitis, generally speaking, it's going to be your urgent cares and emergency departments, women's clinics, OB/Gyn, even your primary care clinics, things of those types of patients. So those are the potential stakeholders that you will want to have conversations with if you are considering bringing them a rapid molecular assay.

Of course, with your lab team, you're going to want to involve your pre-analytical, so those are the folks who are collecting specimens and processing your specimens, then of course your analytical staff. And maybe this is an assay that you maybe run in more of a general lab setting, or maybe you are a smaller facility and you run everything, you run all the tests, including microbiology. And of course, your lab leadership. It's going to involve a verification study. You will have to involve your medical director and any other medical director personnel, such as medical directors of emergency department or women's service lines.

Number two, you're going to want to manage this project. This is a big project, and if you need guidance, there are resources out there for you, but number one, check in with your lab quality team for guidelines, possibly from your quality management plan. You may have a document that kind of outlines for you the things that you need to do to bring them a brand-new test, so you'll want to write a list of tasks that need to be done, or maybe you have a checklist from your quality department. That's wonderful. That is something that we have in our quality department. And figure out who is responsible for that test, and then an approximate timeline.

And then, think about how many of the tasks are going to be going on at the same time. This is where this project management kind of kicks into high gear. Enlist help, because you will not be able to do it all. You are going to need help. You are probably going to be doing many of the same things, many of these things, at the same time, so obviously there will be LIS build, you'll have to test, or maybe it's somebody else that does testing. You will have to create a charge code, so you're going to have to figure out what your costs are to run the assay. You'll need to provide education to your stakeholders and your lab teams. You'll have to do training in competency, and then collection device changes, that sometimes is really challenging.

If you're considering an assay that is going to potentially have a change in collection device, you'll need to consider who it is that orders your collection devices. It might be you and the laboratory, and you supply them, or it might be your nursing partners that will order and stock those supplies in their respective areas. If that's the case, you're going to want to get education out to them in terms of, "This is the supply item you'll need to order. This is what it looks like when it arrives."

Regulatory requirements. Obviously, there's procedures. There's IQCP if you choose to run your assay and not do QC daily rotation testing. Obviously, there's CAP and proficiency testing. Now, maybe whatever regulatory body accredits your laboratory, they will have requirements as well. And then communication is key. You cannot over-communicate, and it gets very important to keep your stakeholders updated, especially if you experience any delays, education, just really open up that channel for communication to stakeholders and your lab teams.

Number three, since we're talking about organisms, group B strep, CT/NG, vaginitis, really involve your infectious disease and pharmacy teams, especially if you're changing targets, such as for vaginitis. Maybe you're going from an assay that has Gardnerella and lacto in it, and now maybe you're considering an assay that doesn't have it. There may be implications for what is used for patient treatment, based on the targets that are now going to be reported, so make sure you pull in pharmacy and infectious disease. And then number four, be proactive, but have a backup plan. For us, when we were implementing MVP, we knew, because vaginal specimens can be kind of an invasive procedure for a patient, and I would not want to have to do a recollect unless we absolutely had to. So for us, we made sure that we had a backup laboratory that could perform the old test, should we get a patient specimen on the old collection device.

So again, if you're talking about new collection devices. You want to order a lot of them, you want to order them ahead of go live. It's not something that you want to think about a week before go live. Like, this needs to be in your implementation plan. And you can arrange for a swap-out of supplies in clinics or labs if you're doing a change in collection device. So again, it's being proactive. It is a lot of work, and maybe this is something that someone in your inventory or supply chain can help you out with, but the more time you invest in that, I think it's going to result in fewer recollects needed after go live.

Check your IFUs. If there are additional devices in the IFU approved, include them in your verification. And what I mean by that is for example, if the IFU says that you can run it off a liquid amines or an e-swab, or you can run it off of a regular culture and swab, if you know that there is potential for your lab to receive both of those types of collection devices, consider including both of them in your verification study. That way, your team is not locked into only receiving one type of device. And again, check your IFUs, and only include what is included in your IFU.

Now, what if a clinic sends an old collection swab? This is a potential scenario. As I mentioned with the vaginal specimen, I hate to ask for a recollect on that, so you'll want to identify a backup lab. And this might be a reference lab for you, if you're more of a smaller facility and you don't really have anyone else to send to, or maybe you're a part of a larger health system, and there is somebody maybe that is going to keep the old assay for a little while. That might be an avenue for you to explore. And involve your LIS, because your LIS team may need to do some reworking of your test in order to do that. And we know that when a patient has to be recollected for a specimen, sometimes it does happen and it is needed, we have an opportunity to affect patient experience and satisfaction scores.

And then lastly, what if you get a wrong test order? Let's say you decide to change tests completely, and now you have not only a new collection device, but now you have a brand new test order as well. Who's going to educate to that, and how are they going to educate? This is obviously going to be tied into your LIS, and the education may not be done by you, or maybe it will be done by you. If you have an externally facing website that lists test collection information and ordering information, you'll want to make sure that you update that, if you have newsletters or you have like an email blast. Whatever method of communication you have for notifying providers of the new test, the new collection device, notifying your nursing partners, and again, being proactive but having that backup plan, is going to pay off for you if you're changing a test, or especially involving a new collection device.

So in summary, today we talked about CDC surveillance data, 2.5 million cases of chlamydia, gonorrhea, and syphilis in 2021, and that's preliminary data from the CDC. We also talked about group B strep, national estimates of disease, as well as vaginitis, vaginitis encompassing bacterial vaginosis, VDC, which is vulvovaginal candidiasis, and trichomoniasis. We talked about rapid diagnostics, benefits to doing that, and things to consider, as opposed to doing batch testing or remaining on culture or wet preps for your vaginitis. We talked about the most common molecular platforms for group B strep, CT, NG, and vaginitis, and then we also talked about key points for test implementation.

It is a large project, a lot of things happening at the same time, and I actually say that, as a laboratorian, running verification samples or just running QC is actually the easiest part of bringing the test live. There's so many other things that maybe not everyone fully thinks about when they are bringing a test live, and it is even more involved if you are changing a collection device, or changing the name of your test. I have all my references listed here. The IFUs can be found at various websites. You can take a look at all of the data that we talked about, and even the studies that were referenced in the presentation. And happy to answer any questions.

Bryan Turner:

Hello everyone and thank you for attending today's webinar. Group B Strep: A leading cause of early-onset neonatal sepsis. I'm Bryan Turner, a marketing manager for Cepheid, and I'll be your moderator today. Before we begin, we want to cover a few housekeeping items. At the bottom of your audience console are multiple application widgets you can use. If you have any questions during the webcast, you can click on the QA widget at the bottom and submit your question. We'll try to answer these during the webcast, but if a fuller answer is needed, or we run out of time, we'll answer later by email. A copy of today's slides are available in the resource widget at the bottom of your screen. You can also expand your slides by clicking on the maximize icon on the top right of the slide area, or by dragging the bottom right corner of the slide area. If you have any technical difficulty, please click on the help widget. PACE Credits are available for attending today's session.

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For those of you just joining us, welcome to today's webinar Group B Strep: A Leading cause of early-onset neonatal sepsis. Today we are joined by two speakers. Dr. Silverman, who currently works at the David Geffen School of Medicine at UCLA, where he has a faculty appointment as a Professor of Clinical OB-GYN, and serves as the director of Maternal-Fetal Medicine fellowship program. In addition to his clinical and teaching responsibilities, he's also the director of the department's new Infectious Diseases in Pregnancy Program. In that capacity, he's working with both adult and pediatric ID divisions, as well as the department of microbiology to develop a multidisciplinary program, to develop educational research in clinical care focus areas. Dr. Silverman has authored over 50 peer-reviewed manuscripts, 20 textbook chapters. And he has lectured widely with particular interest in obstetrics, infectious diseases, recurrent pregnancy loss, and prenatal diagnosis.

Our second speaker is Dr. Pride, who's originally from Nashville, Tennessee. He received his undergraduate degree in biology from Wake Forest University, his PhD in microbiology and immunology for Vanderbilt, and his MD at New York University. He is board certified in internal medicine, and received a subspecialty training in infectious diseases at Stanford. He's a professor in the Departments of Pathology and Medicine at UC, San Diego. Dr. Pride also serves as the director of microbiology laboratory at UC, San Diego Health. His major interests are in developing diagnostic tests for infectious diseases, understanding the role of microbial communities in human health and disease. His research laboratory specializes in human microbiome research for the focus on viruses that inhabit the human microbiome. His laboratory also focuses on understanding how to use bacteriophages to promote human health. And now with that introduction, I'm going to hand it over to our first speaker, Dr. Silverman. Take it away, Dr. Silverman.

Neil S. Silverman MD:

Thank you very much Brian. And thanks to all of you joining me from Los Angeles today to talk to you folks about Group B strep diagnosis and treatment. And to discuss the new guidelines that were issued about two years ago from the American College of Obstetrics and Gynecology regarding preventing Group B strep disease in newborns. My disclosure information is listed as you see it there.

So as background, what we're primarily going to be talking about is the guidelines that are designed to prevent early-onset GBS illness in newborns. Which is still the leading infectious cause of neonatal sepsis in the United States. This was first identified actually in the 1970s as a leading cause of sepsis. And in those early studies, maternal colonization with GBS was identified as the primary risk factor for the development of significant newborn illness. Before any of the guidelines were established back in the 1990s, the annual incidence of this illness was about two cases per 1000 live births in the United States. And since the guidelines have been introduced and refined over the past 30 years, that rate has been decreased to under 0.25 cases per 1000 live births in the United States. What we know is that the primary risk factor for neonatal early-onset disease related to GBS is maternal vaginal-rectal GBS colonization during labor.

Now, that's not to say that GBS in itself is a pathogenic organism in ordinary circumstances. We know it's a physiologic component of both the gastrointestinal and vaginal microbiome. And that the GI tract is the reservoir, the source, for maternal genitourinary colonization. However, colonization in this particular region in the body in general can be transient or persistent. And that studies have demonstrated that the prevalence of being colonized in pregnancy at any given time, including in labor, is about 30%. What we also know is that of the pregnant individuals who are colonized in the first trimester, only about a third of them will be still colonized at the time of delivery. So that's why the very early guidelines tried to develop a way to test folks during pregnancy in an appropriate manner that would be most predictive of their colonization status at the time of delivery.

Neonatal GBS illness is typically presenting on the day of life, or the first day of life. And 95% of these cases in infants occur within the first 48 hours. Early-onset disease in general is defined as illness that occurs within the first seven days of life. After seven days of life, it's termed late-onset disease. And that's actually a very different illness, and not what these guidelines are designed to address. Kids tend to present with sepsis, pneumonia, or less commonly, meningitis. Interestingly, the majority of these cases, almost three quarters of them, occur in full-term newborns. And GBS accounts for almost half of confirmed sepsis in this group of full-term babies. In the very early stages of identification of GBS as a source of illness, the case fatality rate, meaning the number of infected newborns who actually died, approached 50%.

Currently, with the introduction and adoption of management guidelines, about 2% of term infants will still have significant illness, including mortality, if they are colonized. But almost 20% of preterm infants will have mortality related to newborn illness. So it is an important thing to identify a risk for in all newborns, but particularly in preterm newborns who are more susceptible and vulnerable. This little diagram basically outlines the overall risk of mother to infant transmission of GBS. So if we start with a GBS colonized mother, about half of those newborns will be colonized and the other half will not. And of those who are colonized, the vast majority of them in a term infant will be asymptomatic and need no additional intervention. But 2% of them will develop early-onset sepsis, or pneumonia, or meningitis. So the maternal risk factors for early-onset GBS disease in newborns, we've already mentioned that the primary risk factor is maternal vaginal-rectal colonization. But also preterm delivery and extended duration of ruptured membranes, or water being broken of at least 18 hours. Or any evidence of clinical intra-amniotic infection during labor.

We also know that women who have asymptomatic bacterial colonization of their urine identified during pregnancy, are at much higher risk of maintaining that colonization as they approach delivery. When GBS gets into the lower urinary tract, it is a marker for heavier colonization. And actually in those individuals we don't even recommend culturing them again as they get closer to term. That bacterial colonization warrants empiric treatment of these folks during labor. And also if a mother has had a prior child affected with GBS disease, that is an additional indication for empirically treating her during labor with all of her subsequent pregnancies.

So having identified in the 70s that GBS was an important factor in neonatal sepsis, the early discussion was who should get screened during pregnancy? And that's where folks like you who work in the laboratory are so important. The initial debate was whether all pregnant people should be screened during pregnancy, or whether the identified risk factors should be the primary reasons that people got screened during pregnancy. It was identified in the 80s that giving folks who were colonized by culture targeted antibiotics during labor was a very effective way at preventing this early-onset disease in their newborns. This was identified in early studies in the 80s. And has been reinforced most recently by a systematic review in the journal Clinical Infectious Diseases about five years ago, showing that intrapartum antibiotics targeted against GBS is really the most effective way to prevent newborn illness. In terms of identifying colonized women and treating them intrapartum, that is really the most effective way to deliver antibiotics.

It has been shown that if you treat people, or culture them, before they go into labor and then try to treat them before labor or give oral or intramuscular regimens instead of intravenous antibiotics, none of those approaches has been shown to be effective. And then once it became established that colonized pregnant women should receive antibiotics during labor, the challenge was how to best identify these colonized women who should receive this prophylaxis.

When we use intrapartum antibiotics targeted against GBS, it's really based on a two-pronged approach. One is to lower the rates of neonatal GBS colonization. Because if a newborn isn't colonized, it won't get infected. And that requires that the drug used achieves adequate maternal drug levels to deal with colonization in the genitourinary tract. And also it needs to additionally reduce the risk of neonatal sepsis if a newborn is colonized. And that requires adequate levels of the antibiotic in the fetus and the newborn. So the current recommended antibiotics and dosages of antibiotics in the guidelines, were developed with the goals of both achieving adequate drug levels above a MIC for GBS in fetal blood and amniotic fluid, while minimizing the risk of maternal side effects and toxicity. So the very first iteration of the GBS guidelines were published by the CDC with input from the National Organizations for OB-GYNs, Pediatricians, and Microbiologists in 1996.

And it evaluated an approach and gave people the option of either screening everybody at 35 to 37 weeks, giving antibiotics for those who are identified as carriers. Or giving antibiotics for those who had preterm delivery. But also gave the option of risk-based approach and using antibiotics during labor only for people who developed risk factors. And in both strategies, prophylaxis was given to the women who we talked about earlier. Who had bacterial colonization during pregnancy, or who had a prior affected newborn. The problem, unfortunately for OBGYNs, is that they didn't really understand or remember what the risk factors were. And follow-up studies after this actually showed that the risk-based approach was clearly inferior to universal screening, primarily because providers missed a significantly greater number of at-risk women using a risk-based approach compared to screening. So this graph demonstrates the impact of subsequent guidelines after 1996 on the rate of early- and late-onset GBS.

And what you can see is that the initial guidelines were here in 1996. And as they started to become adopted, the rates of early-onset GBS declined. And then as subsequent iterations were rolled out, we have a significant drop in the rates of newborn GBS and late-onset GBS. Which is really a different disease, was not impacted. But that is not really what was intended. But really the era of universal screening rather than risk-based screening clearly made a difference in lowering these risks. So the most recent iteration of these guidelines, I had the opportunity to participate in being one of the editors for ACOG of these new guidelines. They were initially published in 2019, with a interim update and the final version in early 2020. And what we did is we changed a few things with folks like you in the lab will be seeing.

Initially we had recommended that GBS screening be done between 35 and 37 weeks gestation. And that's because studies suggested that the greatest predictive window for these pre-delivery GBS cultures was about five weeks. That was initially reported in the late 90s by the group at University of Florida using culture-based screening. And more recently by a group out of Finland, about three years ago looking at PCR-based pre-delivery screening. And both of those, using both culture and PCR-based screening, demonstrated a culture to delivery predictive window of four to five weeks.

And that that predictive window dropped significantly if the culture was done too much before delivery, certainly after five weeks. So when we evaluated the data for this new set of guidelines, we changed the screening window a bit to 36 to almost 38 weeks. And the reason for that is, if someone were to come in in labor prior to 36 weeks when they wouldn't normally be screened, the default would already be to treat them during labor because they were delivering prematurely. And this would provide a five-week window for a valid culture up to 41 weeks. And in the United States, there are many more women who deliver at or beyond 41 weeks, than those who deliver between 35 and 36 weeks. So we are actually getting more women falling within the valid predictive value when we move the screening window by just a week later, so that the cultures would continue to be valid up to around 41 weeks.

Part of the guidelines that directly impact laboratory personnel really have to do with how these tests are ordered and processed. We very strongly emphasize in the guidelines that when these vaginal-rectal swabs are being obtained, whether they're culture or whether they're PCR, they have to be marked as coming from a pregnant woman. And any penicillin allergy that that person has, needs to be noted on the laboratory request. Whether it's a paper requisition in a given institution, or more commonly in the electronic medical record. These swabs need to be done from more than one site that sampling only the vagina, for example, significantly lowers the sensitivity of culture and PCR by about 20%. So these need to be vaginal-rectal swabs. And recent studies have demonstrated that among providers incorrect sampling, typically vaginal only and not sampling the rectum, is the most common screening error. And we try to teach our residents this and we try to emphasize it when people like Dr. Pride and I give grad rounds. However, it takes a lot of repeated emphasis of how to do things properly.

The other aspect of processing is that the labs need to know that these are GBS screening swabs, so that these swabs need to be incubated first in a selective enrichment broth to optimize the sensitivity of results. And this applies both for culture and for PCR. And then if a woman reports a penicillin allergy that is significant enough to not use penicillin or a cephalosporin, then clindamycin susceptibility testing needs to be done for those individuals who report a penicillin allergy to help providers decide which alternate antibiotic would be used if the culture comes back positive. So we are entering with GBS screening the era of molecular testing. And those of you who work in the lab, know that molecular testing is not new for infectious agents. And it has evolved as a first line method for a number of infectious agents, specifically gonorrhea and chlamydia. Which, those of us who are my age, remember actually doing formal cultures for. But now we can do a duplex PCR, either on a swab, or in urine for both gonorrhea and chlamydia. And TB as well, is now primarily a molecular testing modality.

Nucleic acid amplification testing for GBS has been shown in a number of studies over and over again, to be at least equivalent but more commonly superior in sensitivity to culture-based screening when that test protocol includes a pre-analysis incubation step. And in a number of studies, one published about five years ago, shows that the sensitivity of culture versus PCR is culture is inferior to nucleic acids testing. And even though these numbers are close, they are still statistically significant. The caveat here is that rapid testing by PCR still carries with it with GBS a lower sensitivity. And that is why when we evaluated the data when we were writing these guidelines, we strongly advocated for the use of molecular-based testing as a reasonable and potentially more sensitive alternative to culture for antepartum screening, since the results needed to be available within six to 12 hours. And there would be time to optimize the sensitivity of the test by having the appropriate incubation phase before the aliquot in the analysis tube was actually put into the processor.

The other primary limitation with nucleic acid testing for GBS is for those individuals who report a severe penicillin allergy, because since PCR testing does not isolate an organism the way that culture does, you can't do susceptibility testing from the same swab or the same aliquot. And you need to be able to set up a separate culture to do susceptibility testing for clindamycin in folks who report a penicillin allergy. And that's why it's so critical for providers to report penicillin allergy to the lab if NAAT is being used for antepartum screening. We're still fighting to get PCR antepartum screening used routinely. The most recent CDC survey showed that while the laboratory use of NAAT-based GBS screening increased from 2010 to 2016, it is still low overall. 93% of the almost over 500 labs who were surveyed responded, which is impressive for laboratories to actually reply to that degree.

We can't get those kind of results when we screen medical groups unfortunately. And just under 20% actually reported using NAAT. Almost all the labs using NAAT were hospital or clinic-based. And almost all of them reported using the enrichment step, which means that they were using it for screening, not for rapid point of care testing on labor and delivery. And I'm happy to say that my new position in the division at UCLA, I get to work closely with our director of microbiology. And they use NAAT screening for antepartum screening. And that obviously makes me very happy that I don't have to try to militate for it in a new institution. And just why this is so important. This addresses finally sort of the issues that we have with antibiotic stewardship in the United States. We still keep penicillin as the first line agent for prophylaxis in folks who do not have severe allergies.

Ampicillin should still be reserved as an alternative. And penicillin is preferred because it has a narrower spectrum against gram-positive bacteria. And a lower risk of evolving resistance in other organisms that may be living in the vaginal flora. In a CDC surveillance study that was published eight years ago, it was demonstrated that while the rates of GBS neonatal sepsis continued to decrease even one or two doses of ampicillin as a non-necessary alternative for prophylaxis during labor, would cause the evolution of resistant E. coli to ampicillin in almost two thirds of exposed cases. And this really only required one to two doses during labor.

When folks report severe or high risk penicillin allergies meaning anaphylaxis, or more severe dermatologic manifestations, then the first line drug would be clindamycin. If this isolated specimen is susceptible to clindamycin, and if the GBS is clindamycin-resistant, then vancomycin is recommended. This is an important issue because almost 50% of GBS in the United States is now resistant to clindamycin. So that it's very important for us to have the susceptibility information so that we're not using clindamycin empirically with a resistant organism. And basically not treating the mom at all. And assessing penicillin allergy is clearly an important thing for us to be considering. And these most recent guidelines have emphasized the importance and safety of considering penicillin allergy testing during pregnancy, simply because the vast majority of people who report an allergy are actually tolerant at least 90% of the time. So I am going to wrap up that portion of my presentation, and I'm going to turn the floor over to Dr. Pride. Thank you for your attention.

David T. Pride MD, PhD:

Thank you so much for the introduction. It's my pleasure to be here today to talk to you all a bit about nucleic acid testing for Group B streptococcus. You guys have already seen Dr. Silverman provide a much more clinical and guidelines-based approach for Group B streptococcus testing. And I'll provide you guys the perspective of myself, who's an infectious diseases physician, as well as a director of a clinical microbiology laboratory. And I'm specifically at the University of California San Diego. So I'll start with my disclosures. First I am currently a consultant for Cepheid. I have been a consultant for both Roche and Hologic, who have some of the tests that we will speak a little bit about today. So a little bit about Group B streptococcus. As you guys have heard, it is a potential pathogen, but it's also a colonizer, or an organism that lives on the skin, of a lot of individuals.

And in general, it's an organism that doesn't really want to make you sick. And for a lot of pathogens that live on the human body, they tend to become pathogens when for example, they get to places where they're not supposed to be. So for example, with a common pathogen like staphylococcus, it lives on your skin and if you get a cut, or scrape, or scratch on your skin, then that pathogen can get underneath your skin and then cause disease. The same can be said of an organism like Group B streptococcus. It is the only sort of Lancefield Group B known as streptococcus, also known as streptococcus agalactiae. And it commonly lives on the skin. And maybe more important for today's topic is, it lives in the gastrointestinal tract as well as potentially on the vagina of women. And why that is a problem is not necessarily because it is typically very pathogenic in those women. But it's a problem in pregnant women because there's potential for transmission of the microbe to the relatively naive neonate.

So as I was just mentioning, we really are quite concerned about the potential for Group B streptococcus transmission. We tend to be concerned primarily during the process of childbirth, whereas that infant traverses the vaginal tract, it is able to pick up what may be colonizing Group B streptococcus. And then that infant ends up being born with Group B streptococcus, and then has the potential to develop a Group B streptococcus infection. The risk factors, I think you guys have kind of already heard about. The most obvious risk factor is the mother being colonized, but then there's the prolonged rupture of membranes. As well as premature deliveries that are risk factors for Group B streptococcus as well. And, as I sort of mentioned, it's not particularly pathogenic for most of us, as there are many of us, both men and women, who are colonized with the Group B streptococcus.

But where we worry about it most is in the transmission of those microbes to the neonates. According to the CDC, there's about 31,000 or so Group B streptococcus infections in the US every year. The majority of those, thank goodness, are adult infections. Where we worry most though, it causes about 7,600 infections in newborns every year. And it has about a 5% mortality rate. And while 7,600 may not sound like a lot of infants, when you think about a 5% mortality rate on that 7,600 infections, that's actually quite a few infants. We worry most about the early-onset disease that occurs generally within the first seven days of childbirth, but also there's a potential for later onset disease as well. So you could never... Or at least early on, you're not necessarily out of the clear just because that infant or neonate has not developed an infection by day seven.

And the sorts of diseases we may see in children who have become colonized as they are born, is that they may develop bacteremia, sepsis, pneumonia, as well as meningitis. And unfortunately the neonates are not very well-equipped to be able to deal with these sorts of infections. So while disease in mothers is not uncommon from Group B streptococcus, it typically is not something that is particularly fatal, for example. In young children, unfortunately, the case is a little bit different because they're not well-equipped to be able to deal with it. And the reason that that's so important is that Group B streptococcus is incredibly susceptible to antibiotics. We don't see a whole lot of organisms nowadays that are still susceptible, for example, to basic penicillin, which has been around for a very long period of time. Group B streptococcus remains highly susceptible to penicillin. However, sometimes you just can't deliver penicillin fast enough to be able to prevent morbidity and mortality in those neonates.

So as Dr. Silverman was saying, protocols have been developed for the treatment of Group B streptococcus. And the people to treat, I think to some extent, do become obvious, right? Group B streptococcus in the urine, as you might imagine, the vaginal tract, urinary tract are quite close in women. So if you find Group B streptococcus urinary tract infection, or just colonization of the urinary tract, really you need to treat for the potential that that neonate can become colonized. Any women with positive rectovaginal screens, meaning that you're screening what's living in the guts of those women, as well as what's living in the vaginal tract. If you find Group B strep, there's a possibility that that child can become colonized in the process of childbirth. If you don't know, in general, the recommendation is to treat. And there are still a number of women who still don't necessarily get routine prenatal care.

And in those circumstances, treatment really is the best option to try to prevent Group B streptococcus invasive disease. And then prolonged rupture of membranes is also a big risk factor. So you might imagine, with all of these protocols in place, why is Group B streptococcus still considered a problem? It seems like we're sort of perfectly prepared to be able to screen and reduce, as has been already shown, the prevalence of this particular disease. And the problem sort of becomes from a clinical microbiology standpoint, is in general, are we using the best test to be able to determine disease? What is the potential that we can be telling someone that they are negative, when in fact they are truly Group B streptococcus positive? And along with that might come risk to their infant? So the guidelines from the CDC really sort of recommend either Group B streptococcus culture, or Group B streptococcus nucleic acid amplification tests.

So in a lot of ways these tests are treated like their equivalent, and they're not exactly equivalent. It is true though that in the settings of a positive test and you treat, you can significantly decrease the prevalence of disease. But that doesn't necessarily mean that the tests that are available are equivalent in themselves. So there are culture-based tests as we sort of had mentioned. There are nucleic acid amplification-based tests that are also available. At my institution we did culture for a long period of time. And we somewhat recently have switched to nucleic acid amplification-based tests. And we were very happy with the culture that we were doing for many years. We had about a 20% positivity rate on our cultures. Primarily what we would do was we would take a rectovaginal swab as is customary for most Group B streptococcus testing. We take that rectovaginal swab, we do an enrichment step. Meaning that we take the swab, we place it in a media that will preferentially grow organisms like streptococcus, and then you take that enriched media and you try to grow it on a plate.

So that's what we did. And we would take advantage of the fact that Group B streptococcus is a beta hemolytic organism, so we could grow it on a blood agar plate and we could just look for evidence that there's lysis of the red blood cells on those blood agar plates. And that worked fairly well for us. There are also different types of media such as carrot broth, Granada agar, even Chromagar's, that allow you to do basically a similar thing to screen for patients who have Group B streptococcus infection. The problem in general, particularly with beta hemolysis is that somewhere around 4% to 5% of Group B streptococcus isolates are not beta hemolytic. And it's a problem as one might imagine, because if you imagine having a hundred pregnant women, all of whom have Group B streptococcus infection, and the best you might be able to do is to identify 95, 96 of them. Meaning that four or five are probably going to fall through the cracks.

And that's sort of the take that we have had on using culture for Group B streptococcus identification. That there's a small sort of window where you might be missing positives just based on the way some of the tests work. And it turns out that those same isolates that tend to test negative for beta hemolysis, also tend to test negative on carrot broth and Granada agar as well. So it's not really something that can simply be overcome just by changing the way you culture. And now there are nucleic acid amplification tests that are available which work quite well. But with that caveat that in general you're doing it after an enrichment step. So it's not the sort of test in general where you get an immediate answer. It's the sort of test where you take around a day to enrich, and then do a nucleic acid amplification test.

There are a lot of IVD or FDA approved assays for nucleic acid amplification of Group B streptococcus available. There's a test from Hologic, Luminex, there's several tests available from Cepheid. Even a rapid test without an enrichment step is available from Cepheid. And many of them do work similarly, or have a somewhat similar performance. But as we were sort of looking at transitioning from culture potentially to nucleic acid amplification-based test, we decided to do a rather large study really to evaluate how these tests may perform against one another. But most importantly to evaluate how they perform against culture. And we analyzed three different testing platforms. We looked at the Hologic Panther, a version of the Cepheid GeneXpert, as well as a version of the Luminex Aries. And we basically compared them using all of the same samples. And each of these different platforms has different capabilities and one might choose which of the platforms to use just based on the workflow of their own particular lab and the size of their institution, for example.

So at our institution, we do a lot of Group B streptococcus testing. So we really wanted to choose a platform that would allow us to do a relatively large number of tests within a day. So for example, you can see that there's the Hologic Panther, which can do a large number of tests. But there are different formulations of the Cepheid assays. Depending on which formulation you choose, you can do a relatively small number of tests or a larger number of tests. And the Luminex Aries as well has different formulations available that may allow you to do more or less tests. So those are the platforms basically that we analyzed in our analysis of our patient population. And we recruited 500 women, looked at 500 different vaginal-rectal swabs. Again, we subcultured them all using LIM broth. And then we took that LIM broth and we moved it to our standard of care, which is again culture on a blood agar plate looking specifically for Group B streptococcus.

And then we would identify that Group B streptococcus using multi-tall technology. And we compared those on the exact same specimens to different aliquots of that LIM broth tested on the Hologic platform, the Luminex platform, or the Cepheid GeneXpert platform. So in essence, we're comparing culture to nucleic acid amplification test. We're also comparing three separate nucleic acid amplification tests. And what we found, it wasn't terribly surprising, but it still to us was a little shocking when we actually looked at the numbers. We identified out of those 500, about a 108 of them, which were actually positive via culture. Again, right around 20% positive culture rate. And then when we look at those that were PCR positive or nucleic acid amplification tests positive, but culture negative, we could see substantial numbers using each of those tests. Which again was telling us, "Gee, maybe we've got more Group B streptococcus in our patient population than we had originally thought, based on our culture results."

So as we try to figure out, because we're looking at four different tests, which ones are right and which ones are wrong. We sort of decided on a really sort of simplistic consensus analysis to get at what we think are the true positives and the sort of false negatives. So in general, when we have four tests, in essence, if two or more are showing the same result, we would consider those true positives. And if, in essence, just one of the tests is showing us that it's positive, we might consider that a false positive. So in our analysis of culture, we found again, a 108 true positives, but 39 false negatives. And that corresponds to about a 73.5% sensitivity rate in our patient population. And this is similar to other numbers that you can see in the literature, which certainly strongly suggested that we're missing a number of Group B strep positives in our patient population.

When we look at the PCR test, you don't see nearly those numbers, false negatives. And in fact, each of them have a sensitivity right around 96%. And the number of false negatives is closer to five, or six, all the way across. So certainly using the sort of consensus criteria has given us the sense that these assays are more sensitive than is the culture-based technique. And when we saw that, we really sort of had to make an immediate decision that we've probably got to move on from culture. And one of the sort of anecdotes that I would say as to why that's really important to us, is that one of the things that people may not appreciate as much about life in a clinical lab. But for the most part in clinical labs, the people that work in clinical labs know, "This is bad." Or, "This is okay, we can deal with it."

And I can tell you in the clinical lab, every single time we see a neonate that's born and we get a Group B streptococcus culture that's positive from blood, or from the cerebral spinal fluid, or even from the lungs, everyone hearts sinks here. We realize the importance of it. And part of the reason that hearts sink over here, is that we realize that this is potentially preventable. If we're using highly sensitive tests to be able to screen mothers as best we can so that they could be prophylaxed properly against it, this is something that can be prevented. So that's sort of the way that we look at it in the clinical lab. So when we saw that number of 39, it was not something that we felt we could move forward with at our institution. When we look specifically at CT values, again, it's sort of the cycle threshold where a test becomes positive. The lower the CT value in general, the more reliable the result typically is going to be. And the more likely you are to have multiple different tests that give you the same sort of answer.

When we look at our true positives, the CT values are lower, somewhere around 20-ish. And for our false positives, they're much higher, closer to 40. And the one thing to keep in mind is just as a generality, CT values less than 30 are usually when there's just a lot of the organism around. CT values around 31 to 36 usually are more when there's a moderate amount of the organism that is around. So our CT values of around 20 or so, are telling us that there's a whole lot of this Group B streptococcus around in these patients where we're detecting it. And we can see that when we just look at concordance amongst our testing methods. When all four methods agreed with each other, generally the CT values were right at around 20, and in some cases below. Again, telling us that in order to get concordance, we have to have high amounts of the microbe present. When we see the three nucleic acid amplification tests that all agree with one another, in general, the CT values are right around 30.

Again telling us that we've got a relatively high to moderate amount of those microbes that are present. And that's sort of what has kind of concerned us, right? The idea that we could have high to moderate amounts of a microbe present and yet still miss it on culture. And that's what got us really to make the switch to Group B strep nucleic acid amplification test. And it's why we strongly suggest that others around the country in their laboratories make those switches as well. The one thing we are not absolutely certain of, is when you get a CT value of 37 or 35, how likely is that baby to be colonized, to become a problem? But we know that the risk is not zero when these tests are positive. So that we feel like moving to nucleic acid amplification assays are really going to be the best modality to help us stamp out disease as is best as possible.

So at our institution, we made the switch right around 2019. And before we had had a positivity rate on our Group B streptococcus cultures right around 18%, maybe a little bit higher than 18%. Since we moved to nucleic acid amplification test, our positivity rate's been at about 20% to 21%. So it's not, maybe as much as you might have expected from seeing the previous figures, but it's still a lot of patients. It really is. We do a fair number of screenings at our institution. It's a lot of people. And it does amount to potentially hundreds of missed Group B streptococcus calls that are not missed at our institution anymore. The other thing I do just want to bring up is that screening, as Dr. Silverman I think has told you guys earlier, is really, really important. And the one thing that really has come across, particularly at our institution, but really all across the world is 2020 when we were dealing with probably the biggest part of the Covid-19 or the SARS-CoV-2 pandemic, there were fewer screenings.

We could see it in our data. Everyone else is seeing it in their data. The positivity rate didn't really change at all. There were just less women who were being screened during that time. There were still plenty of pregnancies. It's just less women getting that sort of routine prenatal care. And that should sort of concern us all because again, this is a disease that is potentially preventable in most circumstances. So not getting screening can potentially lead to more Group B streptococcus disease. So with that, I'll just sort of summarize what our findings and take on Group B streptococcus is. One is that, of course we saw a dip in 2020. Thank goodness we've recovered, and I think we're back to sort of our baseline in terms of numbers of tests. The positivity rates, we definitely saw an increase of a percentage or two. Which actually at our institution corresponds to a relatively large number of patients who can be treated against Group B streptococcus.

We know that pretty much every Group B streptococcus culture we can detect with nucleic acid amplification test. And we had a number of Group B strep positive nucleic acid amplifications in our own institution that sort of really helped us make the decision to move away from culture and towards nucleic acid amplification. And for the most part, most of the nucleic acid amplification tests perform very similarly in our analysis with a similar number of potential of false positive results. So which platform you choose at your institution, I think in a large part, can really just be based on what works best for the workflow and for the patients at your institution. With that, I will sort of like to acknowledge the folks who've been involved in our studies. And turn it over for a Q&A session.

Daniel Williams:

Hi everyone. My name's Daniel Williams, Senior Editor of Industry Content at MGMA. Welcome to today's webinar, From Pandemic to Tripledemic to Endemic: One Practices Transformation Through In-Office PCR. Thanks so much for joining us.

Also, we'd like to thank Cepheid for their sponsorship. Please visit their website at Cepheid.com/mgma, where you can learn how they're game-changing RT PCR platform can help your organization increase practice efficiencies, patient satisfaction, and revenues.

Please see the slide for available credits for the live and on demand experiences. To claim all credit types, you must complete the session evaluation following the webinar. Now, we highly encourage interactivity in our digital events, so please use the chat button to talk to your fellow attendees and the Q and A button to ask questions for the presenters.

Any additional resources such as the slides and session evaluation can be found in the learning management system where you access this program. The education for this session will now begin.

In today's webinar, Dr. Dov Shapiro, Managing Physician at Associated Pediatric Partners will discuss how in-office, rapid multiplex, PCR testing has been a game changer for one pediatric group over the past three years, improving care and boosting efficiency. Dr. Shapiro, I know you have a lot of great information to share with us today, so I'm going to turn this over to you now.

Dr. Dov Shapiro:

Hi everyone. As you just mentioned, my name is Dr. Dov Shapiro. I am the Managing Physician of what is now the oldest pediatric practice in the State of Illinois. This July will be our 68th year in practice. We were also the first practice in the state of Illinois to adopt in-office PCR testing for COVID in our office setting.

So I want to talk to you a little bit about the journey my practice went through over the last three years. And hopefully you'll gain some information for that that can help your own practices moving through these post pandemic phase we're in now and into the uncertain future. I apologize, I'm having a little trouble with the slides.

Okay, I apologize. We're back. So learning objectives of today's meeting, I want to describe to you how my practice was agile and adaptable. And how that allowed us to not only survive but thrive during this COVID pandemic and the times thereafter. And especially how we can deal with that with changing viral patterns that we're experiencing now post COVID pandemic.

I also want to talk to you about how you can incorporate in-office PCR respiratory testing in your office and how that can actually both improve practice workflow and efficiency. And lastly, and from my perspective as a clinician, most importantly, how the impact that testing is on how you make clinical decision making, patient care, and back to life activities for my patients.

So the world's changed. Here we are three years since the COVID-19 pandemic began and none of us could have predicted all the changes that have happened around the world and our country, and especially in the practice of medicine. Nothing is the same as it was before COVID. And while some things have returned to normal, some of us have finally stopped masking, a lot of the things we used to do for medicine and practicing medicine have come back to normal. Many things are forever changed.

So this is through the looking glass. We're definitely through the looking glass here. We're all mad here. We're in a time now that's unprecedented. None of us could have predicted this five years ago. If anyone would've told us three years ago, four years ago, that there'd be a pandemic that would completely change the way we practice medicine, no one would've believed us. Yet here we are and it's not over.

While COVID has become an endemic now and it's part of our normal viral patterns that we're seeing, the way we practice medicine is forever changed. And I wanted to take you all through the journey that my practice went through over this three year period. And kind of tell you how we adapted, how we pivoted and were nimble. And in doing so, we're able to not only survive the pandemic but actually do better than we had even pre-pandemic.

So these are two of my favorite pictures. This reminds you back at the beginning of the COVID Pandemic. For those of you who were not fans of movies in the '80s, the picture on the left is the former governor of California, also known as the Terminator and Arnold Schwarzenegger wearing a mask during the COVID pandemic. And the right we have Rambo, Sylvester Stallone, wearing gloves, checking out the grocery store.

No one could possibly imagine that these two macho figures would be reduced to masking and gloving, but that's what we all were. There was a period of time where our entire country was masked and gloved that we were terrified. And that was just one of the first things that started, was the pandemic was the fear of getting sick.

Everyone remembers these lines, right? Waiting outside public health clinics for hours on end to be fortunate enough to get a COVID test, then to wait five to seven days to get a result. And until that time, you were out of work, your kids were out of school, you were staying away from all your family members. Hospitals had parking lots as you see on the right, all remembers is waiting for hours in line to get a COVID test.

So my practice saw this and we acted pretty early on to make it that our patients wouldn't have to wait on these lines and wait too long to get tests. And we're going to talk a little bit about what we did to accomplish that in just a few minutes.

Well moving very quickly forward, and it wasn't so quick, it was almost a million deaths in the US alone over the COVID pandemic. But by fall of 2022, the COVID pandemic had started to ease. Was still existing and still around, but hospitals were not being overwhelmed with adults in ICUs anymore.

Instead, a new epidemic developed what we call the tripledemic. And for those of you not in pediatrics, you might not have been familiar with this, but for the pediatric world, this was our August 2020. In October of 2022, that winter there, was a three viral kind of pattern that presented all at once. We had an early flu season, a very early RSV season, and COVID season all at once. Overwhelmed children's hospitals across the country.

Hospitals simply ran out of beds. There were no ICU beds to be found if a child needed a ventilator. Even normal pediatric beds were absent. Kids were being kept in the emergency room for days on end because there were no were beds on the floor to be taken care of.

Therefore, ERs were overwhelmed and kids couldn't be seen. People were waiting six, eight, 10, 12 hours in order to be seen. Doctor's offices across the country and acute healthcare clinics and ERs were just overwhelmed with sick kids having severe respiratory illness all at the same time.

Here are two articles from that time, one from The New York Times, this is our March 2020. And here's one from the CBS News in December, "Tripledemic" severely strains children's hospitals. This was caused by the fact that viral patterns were changed.

We did an experiment with our entire population. We put masks on children for two years and we kept them away from other children even in school. Well for years, we had predicted when virus would come. Flu was a winter illness, RSV was a winter illness. All of a sudden, all these viruses were coming at the same time in early or in times of the year that before had never occurred and they all showed up at once.

And the children's hospitals, which normally don't deal with that much serious illness at once, did not simply have enough beds or enough personnel to manage. So this was our tripledemic. This was our pandemic for the pediatric world and there were a lot of really sick kids. It was a pretty sad, difficult time. People had to band together, lots of private doctors had to go to the hospitals after work to help out. There simply weren't enough doctors to see these kids.

So another effect of the pandemic was the fact due to viral patterns changing, we got overwhelmed, and this kind of thing can happen again. This is what everyone's worried about is when's the next tripledemic? When's the next time that a virus is going to show up with COVID and overwhelm our system?

And now finally here we are in 2023, we're in the endemic phase. COVID is now considered to be part of our landscape. COVID's going to be with us. It's mutating. Thankfully at the moment, the current mutation is not as deadly as the ones that proceeded the wild strain back in the beginning.

We are definitely seeing lots of deaths every day, but nowhere near the numbers we did back in two years ago and three years ago. Right now the virus seems to be taking the most advantage of people with really severe chronic lung illness and the elderly, which is still awful and tragic, but everybody else seems to be doing pretty well with the current COVID virus.

People get sick for a few days and they get better. But once again, if you're elderly or immunosuppressed, COVID is still a dangerous virus. Thankfully the vaccines have mitigated how bad people get sick, and the fact that most people have had COVID already gives us some immunity.

But it is here to stay and experts predict we're going to have seasonal waves. This winter will probably be another COVID-19 wave. Hopefully, won't kill as many people because we're hoping to have some immunity and perhaps even a seasonal COVID shot is in the works, but once again, it's not going away.

As a pediatrician though, even more importantly what's happened due to COVID, is viral patterns have been completely upended. We used to always be able to predict what was coming when. Enterovirus, hand, foot, mouth were summertime. Strep was fall. Flu and RSV were winter viruses and there's dozens of others.

And you knew almost without even checking what was going to come at what time of year and what your children and patients would be presenting with. Well, now that's not the case. Everything's been upended. And while our viral patterns are starting to slowly reset themselves, viruses are still completely unpredictable at the moment. We're still seeing lots of viruses in the wrong seasons that we have no way to predict. And we don't know when we're going to finally get back to this kind of predictability of viral patterns.

Therefore, since multiple illnesses can present with the same symptoms, cold, cough, fever, sore throat, we don't know if that child or what they have. Do they have an enterovirus? Do they have strep? Do they have COVID? Do they have flu? Do they have RSV? Seasonality doesn't help us so much. We have to know sometimes what that kid has in order to treat them.

So why is it so important to know what a child has? Well, it's a great question. If it's just a virus and the kid's doing well, it actually isn't that important to know what they have. However, when there's a lot of flu going around, it's important to know about flu early on.

If a child is high risk or lives with a high risk family member, there's viral treatments that if they're done in the first 48 hours, can significantly reduce the length of illness that a person gets with the flu. RSV, which was so devastating last winter during the tripledemic, hospitalized 10s of 1000s of children.

If you can detect that early and you can actually know which children are higher risk, you watch those kids more carefully, you keep them out of the ER. You treat them at home and if they do need to be hospitalized, you get them in early and get them the help they need. So avoiding ER visits, avoiding hospitalization is one of the benefits of knowing what child is RSV.

And then for COVID, once again, while the children themselves are doing well, if they live with grandparents or if elderly grandparents tend to visit, if you know the child has COVID, you're not going to have grandma and grandpa visit. So by just preventing those contacts, knowing what a child has does help.

And lastly, and this is something that has changed a lot, and I'm going to talk about that in the next slide, is better patient satisfaction. For better or for worse, our patients now know what the PCR exists. They know that we're now able to detect what their child has. And especially when their child is acting really, really sick and they're worried about their family members and about their child, more and more patients and families are insisting that we find out what their child has not simply say that they have a cold.

So things have changed due to COVID, due to the tripledemic, and now due to the endemic. First of all, one thing that's become very clear is patients no longer accept the fact their doctor's office can't test for what they need. With the advent of urgent care centers and ERs and all types of ancillary places people can go to get care besides their doctor office, if you can't test and prove what your patient has, they're going to go elsewhere for their care.

It doesn't matter if you're their doctor, it doesn't matter if you have a trusting relationship, if you can't give them the answer they're looking for, they're going to go elsewhere. And at that other place, may or may not know that patient quite as well as you do. So it's to your advantage to be able to offer the test your patients need in your office.

Patients want an accurate result. Patients are familiar with the term PCR now. Three, four years ago, 95% of Americans never heard of PCR. It might even be higher, it might be 98% of Americans. Nowadays everybody knows what PCR is and people also know that the home tests, the rapid antigen tests are not that accurate. They use them in a pinch, but when it's a serious issue, they want a PCR test. They want to know what they have or don't have.

Patients are no longer willing to wait in line for hours and wait a week to get their results. They know the technology exists to give them quick results in a half an hour or less. They want that result and they want to know right away. Another thing that's happened, especially in the more pediatric world, is because for so many years of COVID and then the tripledemic in pediatrics, parents are very, very nervous, more than I've ever seen in my 21-year career.

And people that are coming in early. Even if we tell them they can wait a couple days, if their child has a fever, if their child has a cold or a cough, they're not waiting two or three days to come in, they're insisting on coming in that same day. So we have to be able to accommodate those patients. And so we have to work our practice flow to accommodate extra visits.

If we now, once again, extra visits are good for the bottom line and running a practice, but if you don't do it efficiently, you're just going to piss off your patients by keeping them waiting. So it's important to be able to accommodate those patients, and at the same time maintain an efficient workflow in your office. So in order to deal with all these changes that have come so far and that will continue to come, it's really important that we be nimble and adaptable.

The quicker you can pivot, the quicker you can change and adapt to a new situation, the better off your patients are, the better off your practice is going to be. I'll talk in a few minutes about how my practice managed it, but while practices were pretty much shutting down in the beginning of the pandemic because they couldn't see patients, my practice was open.

As soon as the stay-at-home order was lifted, we were open the very next day seeing sick kids in our office because we had the equipment to test them. Our patients felt comfortable. We had the processes in place to see patients, healthy and sick separately. That our healthy checkups knew they wouldn't be exposed to some with COVID in the next room because there was no one sick in that room at that time of day.

So we adapted and we continued to adapt and we are continuing to adapt as things change. And being nimble and being adaptable is the key to survival in this now post pandemic, what we call the endemic phase of COVID.

Okay, let's go back now. Beginning of the COVID pandemic, I showed you the slides of all those people waiting in line to get tests. We realized that we would have to offer a test in our office. So initially I looked at the rapid antigen tests, many of which you now have in your own homes when they were finally given out for free by the government. Unfortunately we discovered pretty quickly those tests are not very accurate. They're not bad, they're quick.

But like many other rapid antigen tests, their sensitivity is pretty low. The best rapid antigen tests at most are 60, 65% accurate. That means they're missing one third of cases, and for many diseases that's just not good enough. You don't want to be wrong 33% of the time. So we realized we had a do a molecular type test. We knew that PCR was the best technology out there, but we even needed to figure out what PCR system would we use.

So we started looking at a lot of different options. At the same time, we also realized at the time that COVID-19 was not the only virus out there. And that was a very present decision we made because sure enough, the tripledemic proved to us that you can't have blinders on. You can't only look for COVID-19, you can't only look for flu. You can't only look for RSV.

When a patient shows up to your office, with the seasonal variations being upended, you have to pay attention. And so often during this pandemic, people would come to an urgent care center or someplace other than their primary care office and they'd rule out COVID, rule out up strep, and send them home. But what did they have? Were they okay? Were they wheezing? Did that child need further assessment? That wasn't always being considered in the rush to rule out COVID.

So we realized we wanted to figure out what our patients actually had so we could provide better care. So I did a lot of research and it became very quickly obvious to me that one system had the best reputation on the market, and that was Cepheid's Xpert Xpress system. Cepheid's gene Xpert system was pretty amazing for my practice.

First of all, and this was the part that sold it for me, if you look at the slide below, you'll see positive percent agreement and negative percent agreement. For the purposes of this talk, that refers to sensitivity and specificity. So the right-hand column, negative percent agreement, means if you get a positive result, how likely is that to be accurate? In other words, how likely is this to have a false positive? And the answer is it's 0%, 100%. And by the way, that's not uncommon. Most tests are pretty good at only telling you have a disease or an illness if you actually have it.

And sure enough, the Xpert Xpress system is also 100% accurate when it comes to COVID, flu A, flu B, and RSV. If you have a positive test, you have COVID. It's not a false positive, it's real. What differentiates the tests? Rapid antigen tests, molecular tests, and then this PCR test that is gene expert test, is the positive percent agreement, the sensitivity.

As I mentioned earlier, most rapid antigen tests are at best 60, 65%. That means that when they say you are negative for COVID that you don't have COVID, they could be wrong 35% of the time. That's a really high number. Rapid flu tests, the ones we've used up until the last few years, also in the mid 80s, 85%. Better than COVID but still missing 15% of flu. RSV also in that range as well. I'm pleased to say, and this is born out in my own practice, that Cepheid system is near 100% on all four tests.

So flu A, flu B, RSV, are as close enough to be a 100% as to B perfect. And even COVID is in the upper 99 percentile. So essentially in the 1000s of tests we've run over the last three years, I've had one single case where a child tested positive a day later on another platform. Every other case that was negative was truly negative. They did not have COVID.

This test has been nearly perfect for us. So much so that all the local hospitals have adopted it as their system that they use to test in the hospital lab because it is considered to be now the gold standard. So we guessed really right on this one. Another thing that's beautiful about this machine is that in addition to be able to run COVID, flu, RSV by themselves, they also can run all four at the same time on a single swab with a single cartridge. I'm going to talk more about that in a little while. So it gives you the flexibility to decide what your patient needs and then to detect what they have with one swab.

So this is what the system looks like and I'm a big fan because it's really helped my practice. This is an example of machine that has four modules. You look at the picture, on the bottom there, you see that little cartridge and there's four doors. One of them is open, each one's a separate module. Each module functions like its own machine. You can run any kind of test you like in any module independent of all the other modules and you can do them simultaneously.

You don't have to wait to load all the tests at once. You can start with module one and test for flu. And then your nurse walks out of room two. She swabbed a patient for COVID, RSV, and flu. You go ahead and put that one in the second module and start that one running while the first one's already been running for eight minutes.

Next kid you think has strep, you can put a module in there, swab them, put a module in there. That one's running. You can do up to four at a time. And as the first one comes out, you're already ready to reload the other one. This comes in different sizes depending on your needs with a different number of modules. Each one acts by itself.

What's amazing about this system is how easy it was to use. Literally my entire staff trained in less than an hour. In less than an hour, every member of my staff was completely proficient in using this machine. It is made so easy to use.

Literally you type in the patient's name, there's a barcode on the module that you scan into the system. You enter the patient's information, you go in the room, swab the patient, put it in the solution, put the solution in the cartridge, and insert it. The entire time, from the time that specimen comes to the lab, until a machine is actually running a specimen is less than one minute. And then you can walk away and do your next patient and it runs by itself and it shows your results after the amount of time you need to wait.

Depending on the test, it could be 18 minutes, it could be 30 minutes, but it's running independently. It's really a walkaway system. You don't need to spend your whole day by the machine. You put it in, you leave and go do something else. Very accurate as I told you. Very sensitive and very, very easy to use for my staff.

So it's really been a godsend when it comes to efficiency in the office because we can see multiple patients in a short period of time. My office often will now see anywhere between 16 and 25 patients in an hour and a half sick visit. And because of this machine, we can get tests on all of them and get it done the same day and give them the results they need.

Okay. In addition to testing for respiratory illnesses, I mentioned flu A, flu B, RSV, and COVID. This machine also tests for strep for strep A. And why is this so important? For my entire career, the way we've tested for strep is you do a rapid strep test. I'm very familiar with those. They're called rapid antigen tests. If it's positive, great. If it's a negative, you got to send out an overnight culture, which takes up to two days to result.

You have to follow up with the result. You've got to call the patient, inform them if it's positive or not. Patient's waiting for two days to know if they have strep. If they do, they've got two more days out of school or work. Your staff has to make sure not to miss the culture results, to keep tracking them down at the different labs.

Took a lot of time and the patient wasn't happy because they didn't have an immediate result. This particular system is so sensitive, they actually claimed 99.4%, which is actually what I've seen in real life. It's nearly 100% accurate that you are not required to do an overnight culture.

So if you get a negative result on this strep test, there's no backup culture, you're done. Patient, you don't have strep, go home. If it is positive, it's nearly perfect. So once again, this system has made it unnecessary for us to overnight cultures. We can tell a patient definitively in a short period of time if they have strep or not, it can be as little as 18 minutes as they average it tells us to have a definitive answer for our patients.

This has really saved my staff time. It's made us more efficient. It's made my patients thrilled to know for the first time they know with absolute certainty whether the child has strep or not.

And for those of us in clinical practice, you may be aware, the last two months has been a strep epidemic. It's everywhere. Strep has been spreading like wildfire and this allowed us to really get control of that and start antibiotics early on the kids who have it. And not use antibiotics on the kids who don't.

Unfortunately many doctors when they think a kid has strep but they can't prove in the office will put a kid in antibiotics waiting for a culture, if a parent's insistent. We never have to do that because we know definitively if they have strep in the office. So this is not only good in getting early treatment, this is good for antimicrobial stewardship. We can avoid the unnecessary use of antibiotics by being certain if a patient has strep or not in the office.

So how has this helped my practice? I've mentioned to you that while other practices were having reduced visits, we were busier than ever and we were able to accommodate all our patients by having the ability to give definitive testing in the office. Not only were we able to accommodate them, they wanted to come to us. They knew we were a better place to come than the ER or an acute care clinic.

Because while other practices were not seeing sick kids, they didn't have this technology and they were sending all their patients to urgent care or ERs to be checked, our patients were bragging that, "Our doctor sees us in our office the same day." And we were able to accommodate them all. So we didn't lose visits, we actually gained visits. People were coming in earlier with sick kids and they were coming to us instead of going elsewhere.

My practice has always taken patient satisfaction very, very seriously. We have actually two different surveys from two different companies that we use in all our patients randomly which one we choose, to get a sense of how our patients are doing and how they think of the care we're providing them. I've been proud that we're normally in the mid to high 80s, although since COVID started and we actually started doing these testing in the office and offer people same day visits to see them, our scores have stayed in the high 80s. Our last month was actually 97%, which I'm very proud of.

And over and over again our patients mentioned the fact that they could be seen in their office and given the same day result, was key and instrumental in why they like our practice so much. By being able to quickly and accurately diagnose the cause of patient's illness, you can make earlier, better, and more efficient decisions that provide better care to your patients.

You can get your RSV kids monitored or treated as early as possible to prevent hospitalization or ER visits. You can get your flu kids who need it due to risk factors, on medicine in the first 48 hours. And you can get your COVID patients away from the grandparents and the elderly whom they can infect. You can diagnose strep early and you can therefore prevent unnecessary use of antibiotics and treat strep early and get those kids back to school and the parents back to work.

This was not the reason why we did this. We got into this as we always have, to provide care to our patients. We're all physicians. We all are committed to doing the best for our patients. But you know what? Everyone's got to eat. Everyone's got to run a practice. We have payroll to make. And I have to say that in the 20 plus years that I have been the Practice Managing Physician and Practice Manager of my practice, this has been by far the most profitable three years that I've been doing it.

And that has been to a great extent due the fact that we're able to accommodate more sick visits and the excellent reimbursement for PCR testing. So once again, it isn't why we did it, but it doesn't hurt that not only have we provided better our care to patients, but we've gotten reimbursed for it and we've actually done better on the bottom line. So to me this has been a no-brainer.

Over the years as the managing physician, I've made a lot of technology purchases. My practice does like to be on a cutting edge when it comes to technology. Sometimes I've guessed right and sometimes I've guessed wrong and made capital purchases for equipment that unfortunately we haven't used. This one has made me look really good with my partners, this one has been an obvious right choice. So much so that here in Chicagoland, this is what everybody's using.

Nearly all the acute care clinics, all the large children's hospitals, this is a system they finally adopted. And those practices that I know of that started with another system, most of them have switched over to Cepheid system now because it can test for all four viral patterns, all four viral infections. It can test for strep and it's the most accurate on the market.

So there are still some practices that haven't made the switch yet, but every day I'm hearing of new practices that are switching. And that's driven by the fact this test gives you better results than the other tests. I didn't speak about why that is and why it's the gold standard, but that's because Cepheid tests for more different types of genetic mutations compared to anybody else. So they're not checking for one thing, they're checking for three different things to pick up COVID, therefore they're able to pick up so sensitively, even mutations of COVID as well.

So Cepheid is now the gold standard. There's no one out there that I've met who can argue that there's another system out in the market that's meant for office use that's better. This system is so good, it's used in the hospitals now. This is the gold standard. And not only is the gold standard, but it's going to improve your practice efficiency and it's going to improve your bottom line. So for me, this has been a life-changing.

I mentioned in the beginning about being nimble and being adaptable. This is the machine that's letting me do that. And they're constantly adding new tests and as a result, that allows us to continue to be nimble and adaptable as new diseases develop. As existing diseases become testable, Cepheid's adding those kinds of cartridges to their machine, which allows us to continue to adapt to changes and provide the care our patients need in our office setting.

If any of you have any questions, these are two websites. One is a Cepheid GAMA team and the other is the codes for all different kinds of reimbursement from private insurances, Medicare, and Medicaid, all of whom to cover this test.

I'm now going to open for any questions anyone might have.

Daniel Williams:

Yeah, Dr. Shapiro, thank you so much. Great presentation. Really appreciate that. And did want to let everybody know we've got a robust amount of time for Q and A, so about 20 minutes.

So anyone who's got those, please use that Q and A button down there at the bottom of your screen and just drop those questions in there while we've got Dr. Shapiro. So we do have several questions here already. So first one up, are the payers paying for the four-in-one test? Talk about that payment process and how that works.

Dr. Dov Shapiro:

That's a great question. So one of the nice things was during the pandemic when everything was federal government was still in the pandemic phase with the EUA, all insurance companies were required to pay for the test, so they were reimbursing actually very well for the four-in-one. All insurers.

I don't do Medicare, but I know from other practices that Medicare reimbursed as well. But I do do Medicaid and I do almost every other private insurer. Everyone has been reimbursed and the one exception has been HMOs. Most HMOs require to do the test at their lab, so they wouldn't allow the testing. But all the PPOs and Medicaid have been reimbursing for the four-in-ones. And even over the last month, now that the pandemic is over and the government is no longer guaranteeing or enforcing insurance paying for it, we're continuing to get reimbursed by all our insurers.

Nothing has changed. We're still getting paid for these tests just like before. The only difference is before during the pandemic, it didn't apply to people's deductible. One of the rules was that insurers had to cover a COVID test and it was something they had to cover before deductible. Now like any other test you'd order on a patient, a strep test, a blood test, a blood count, the COVID test does go towards their deductible.

But it is not unusual for patients because they're used to that with all testing they get. And patients when they know they can get a result the same day, so far have not bought to the idea of paying for it. If they want to know what their kid has, they understand that it's not free. And once they've met their deductible, the insurance company pays for it.

Daniel Williams:

Okay, thank you so much for that. Next question that's come in, are the tests stored in a fridge or in the RT? I mean how does that get stored?

Dr. Dov Shapiro:

The cartridges are room temperature stable. We literally have them in boxes on a shelf and we have backup boxes in a side room. They don't require any refrigeration, any freezing. There are simple to storage. No, you don't need any storage capacity, just need a place to put the boxes down.

Daniel Williams:

Okay. As far as space, because that can be a challenge for some practices, then how big is this instrument? What is the size of it? And where do you keep yours?

Dr. Dov Shapiro:

I love that question. I thought it was going to be some huge machine. It actually isn't. If you can imagine back in the olden days, those little small laser printers that weren't the giant ones that did everything.

Daniel Williams:

Right.

Dr. Dov Shapiro:

It's about yay tall and about yay wide. This fits a small footprint in our lab. This doesn't take up a lot of space at all. Now they also have ones that are smaller with two modules, but this is the general size. It's about trying to describe it, about a foot, foot and a half tall, about three quarters of a foot wide, maybe a foot wide. Doesn't take up a lot of space at all. So it hasn't been an issue at all.

So space has been no issue. I've been debating over the last month or two about actually getting a second machine to run even more tests. This machine runs so quickly and so efficiently, I haven't needed to yet, but I'm actually been in discussions with Cepheid about getting a second machine. We have two offices, for both of our offices just to be able to run more tests.

Because like I said, it's an awesome machine and if I can do more tests, I can see more patients. So no, this does not take up a lot of space at all. That's one, no matter how small your lab is, this machine's going to fit in there.

Daniel Williams:

Let's follow up there then. As far, you're saying you're already contemplating potentially, or down the road getting a second machine. What would be the threshold then? You were talking about right now it's running efficiently, but the patient volume or the kind of tests you want to run. So how you can get to it? Go ahead.

Dr. Dov Shapiro:

These tests are not instant. Depending on the test, it's 18 minutes, it's 30 minutes.

Daniel Williams:

Okay.

Dr. Dov Shapiro:

So it's really a volume question. I can run four tests at a time. So we have two offices. If we had one office, we would've had two machines already a long time ago. We couldn't have handled the volume. Because we split our sick visits between two offices, we're able to manage by moving those sick visits throughout the day. We're able to manage to do all our tests on our machine throughout the day.

However, my office is still a little bit old-fashioned. Ever since COVID, we've kept our sick hours separate from our healthy hours. I know a lot of doctors aren't doing that anymore, but our patients have expressed interest. They like the idea that sick kids are not coming in next to their healthy baby in the next room.

So we've divided up our sick hours now first thing in the morning. We have another sick hour between 1:00 and 2:00 every day, and then we have another one at the end of the day around 5:30 for a half an hour. So that's when we do all our testing.

So at the beginning of the day, it's no issue. We can run the tests throughout the day. But those end of the day tests, if I have more than four or five patients, I can only run four at a time. That creates a little bit of a challenge where I'm waiting around for test results. So for that reason, we were debating if we get busy enough with sick, having a second machine might let me run more tests at once.

If you're an office that runs sick visits throughout the day, that's really not an issue for you because you can actually run them throughout the day. There's no rush. For us because we're bottle-necking our sick visits into separate times during the day to keep sick away from healthy, sometimes volume becomes an issue if we're busy enough. And if our volume is enough, we're going to get a second machine to handle that volume.

Daniel Williams:

Okay. Let's go to the next question. Just remember there are some great questions coming through, but just punch that Q and A button down there at the bottom of the screen and just drop questions in and keep them coming. They're great. This is a good one. Can you explain why EAI rapid tests are not accurate? What's going on there?

Dr. Dov Shapiro:

It's a great question. So rapid antigen tests, actually unfortunately, and this is true for every, and I'm not a pharmaceutical or an engineer, so I don't know how all the details. But remember rapid antigen, essentially there's a protein that you're attaching to that makes, it's like a pregnancy test.

If you don't have the exact protein that it's looking for, you're going to miss. And you're also relying on the visibility of that line. That's why rapid strep tests miss. With PCR, you're taking into what you have and the microscopic amount and you're amplifying it. With the rapid antigen, there's no amplification, it just has the little amount of protein that's there.

So if the antigen you're testing, for the protein antigen you're testing for, is in small amounts, a rapid antigen test is not sensitive enough to pick it up. Just like a pregnancy test, if you do it too early, it'll be falsely negative. There isn't enough of the hormone in your body to test for. Same thing with a rapid antigen test. If you do it and there's not enough virus protein to test for, you're going to get a negative result.

With PCR, even a minuscule amount gets amplified and then the machine's able to pick it up. And that's why PCR amplification has become the gold standard for viral testing. Because you don't want to wait until they're really, really sick. You want to catch it when they're just starting.

Daniel Williams:

Okay. Let's see, more questions. Let's see which one we're going to go with first. We are seeing high levels of strep. How should we test patients that have recently been positive but already completed antibiotic treatment?

Dr. Dov Shapiro:

This is actually a great question. I'm going to tell you what my office did. Now this is an extremely, extremely sensitive piece of equipment. So the rule that we have figured out in talking to infectious disease doctors and to Cepheid's clinical team is as follows, if you have had strep in the past 30 days and been treated, it is not a good idea to use this machine to test for strep again.

Because this thing is so sensitive that even if a little bit of strep is still left in your system, it might be dead, it could pick it up as be positive. If it's more than 30 days, you absolutely use this machine again. So in those rare circumstances where someone comes in and says back to strep again in less than 30 days, I don't even do a rapid on those kids.

I actually send out a good old-fashioned culture for those kids. Because I need to make sure if there's live strep in their body, not just dead strep in their throat. And this machine is so sensitive, like I said, it could give you a false positive on those people. So for those kids, we do not use the machine unless it's been 30 days or more.

Daniel Williams:

Okay. Got a couple of questions. You and I, Dr. Shapiro have talked about this before, but just we're seeing people don't like to use new normal, but we're seeing a new normal as far as viruses being seen year round. So why was RSV so bad this year? And will it be bad again? What's going on there?

Dr. Dov Shapiro:

There's two parts to this. And by the way, we're hoping there's a bunch of new RSV vaccines that are coming close to fruition. One is for adults, another is for pregnant women, and a third that's going to actually be for babies. For all babies. And I don't know if they're going to come out before this RSV season, but that might help to move the needle a little bit.

There were two issues that we think happened. Once again, it's all speculation, but this is what the experts think. Issue number one is it's not just that RSV hit, it's that it hit the same time as flu and COVID all at the same time. But it's actually more than that. For two and a half years we saw no RSV because everybody was masking. There was no RSV season the two years prior.

Normally RSV is a disease we normally see in babies, kids under a year of age. But since for two years, babies didn't get RSV, all of a sudden they all got RSV when they were three years old or two years old and one year old. You had three cohorts of children getting RSV for the first time, triple the number of RSV cases because triple the number of people that didn't have any immunity because they never had RSV before.

We also saw that for the first time, older kids were getting much, much sicker. And once again, the speculation is that if you get RSV as a child and you get through it, the next time you get RSV, you're not going to get a bad case because you have immunity already. Since none of these kids got it before, when they did get, it was much more severe.

So for all those reasons, the change in seasonal viral patterns, the combination of three diseases at once, and the fact that children's immune systems had no experience with this virus, we were overwhelmed. Prior to this tripledemic, I can't remember the last time I put a child over six months in the hospital for RSV. I think there might have been one or two cardiac patients that needed that, but a healthy kid with no preexisting conditions, unheard of.

The hospital were filled of three-year-olds, four-year-olds really sick in ICU with RSV because they never got it as a children. It's good for children to get sick, no one wants their kid to get sick, but our immune systems require us to get experience with illnesses when we're young so they don't devastate us when we're older.

And so in a way I'm glad we're not masking anymore because masking kids for so long actually prevented their immune systems from developing and weren't helping and I'm sure they will. Over time now the kids are getting sick, their immune systems are waking up and learning how to fight disease again.

Daniel Williams:

Wow. Okay. So this is an important, a follow-up here, but very important. The PHE is over, but we're still seeing waves of sick patients. Does the end of PHE signal the end of testing? Just talk about what you're doing in your practice. What does this mean right now? What are some best practices and protocols to take right now?

Dr. Dov Shapiro:

So let's focus for a moment on respiratory testing. Strep, obviously we're testing because that's around right now. So in our practice, do we still do COVID testing? Yes, but not as often as we used to. At the moment in Chicagoland there's not a lot of COVID.

So unless a child has a known exposure or they go to a daycare or school, which not uncommon, that requires COVID testing with COVID suspicious symptoms to return to school. Or unless they traveled or the parent has concerns about an elderly grandparent, we're not routinely doing COVID tested on children right now.

However we anticipate, and we're already preparing for the fact that come the fall, when COVID starts to rear its ugly head again with flu and RSV, we're ready to go testing for all those things. So now unlike before when I was testing in each office 15 to 20 COVID tests a day, a total of 40 a day in my office, we're probably doing more like three or four a day right now and only two in each office. And those are kids that have had exposure, or parents are worried, or they have an elderly grandparent or a school that requires it.

So we're still testing, but not nearly as often as we did before. But I think we're going to get to the point like it was before COVID, where testing is going to be based on what's going on in your community. And what illness are out there, we'll determine what testing is necessary and at what time of year.

Daniel Williams:

Okay. With following up then with the PHE over, how have you treated it as a practice? Are you back to how your practice interacted with patients prior to the pandemic? Or have you instituted some safety protocols, wellness, sickness? [inaudible 00:42:09].

Dr. Dov Shapiro:

Right, so I alluded to this a little bit during my talk. We have gone back in some ways. Four weeks ago here in Chicago land, was when everyone stopped masking in doctor's offices. Pretty much all the hospital and doctor offices stopped masking during healthy visits. It's so nice to see my patients' faces again for the first time.

I have families that I met during the pandemic with babies who are now two, two and a half years old. These were the first visits over the past month that I've ever seen the parents' faces. It was actually amazing. Oh my God, that's what you look like. I never realized. Sometimes good, sometimes bad, but either way you finally. But it's been nice to finally see my patients and their parents' faces again.

So we've gotten back to not masking. We however have not gone back to seeing sick and well at the same time in our office. Our patients have been really happy with the idea that their kids aren't going to get sick coming to my office.

So we still have our sick patients check in from the parking lot. And they get taken right into a room privately, and that is only done at defined slots in the day. In our office it's from 9:00 to 1030, from 1:00 to 2:00, and then at the end of the day. And those kids are taken in one at a time into one of our rooms, one after another. And they're seen at the end of the day or in those different time slots for sick. And then the rest of the day is all healthy checkups.

That way we're still keeping sick apart from well. I don't see us changing your time soon. This might be the new normal for my office because our patients love it. I'm hearing from them all over and over again, how thrilled they are that we can see them the same day for sick, but they're not worried that when they come in for a checkup, they're getting exposed to someone.

It seems to be the new normal for our patients. Our patients I guess are very germ conscious and they don't want their kids getting sick. And so they're demanding we continue and we're willing to accommodate them because it works good for our workflow as well.

Daniel Williams:

Okay. Several more questions coming through and we do have seven to 10 minutes left, so please drop more questions in there. These are great. You've touched on this, but let's maybe go into more detail. Have you changed any aspects of your clinical workflow to use this test? What does that workflow look like?

Dr. Dov Shapiro:

So that's also changed. During COVID, we had an interesting workflow. And by the way, this workflow I'm about to describe is not for everyone. I'm going to take a moment, actually. I used to have a slide about this during COVID pandemic, but since you've asked the question, I'm going to talk about that.

There are in my mind, three potential workflows for dealing with testing in an acute care setting like a doctor's office or an emergency room or an acute care clinic. The first model is the one that's probably most common in urgent care centers. And that is where a patient comes in, if they meet certain criteria, the nurse already swabs them, then they're put into a room. And by the time the medical provider sees them, they already have a result.

The second option is where the doctor or the provider sees the patient first, then orders the test. The nurse comes in, swabs the patient, and then they either wait for the result or they go home and they're called 25, 30 minutes later and given a result.

The last model is the one that we've adopted until recently. And that seems like it's a little extra work, but it actually has worked very well for us. We actually pre-screen our patients before they even come to the office. Our secretaries schedule the appointments. Then during lunch break, we take about a half an hour and call all those patients coming in for the next sick hour slot.

And we quickly get their history and determine what tests they're likely to need and then pre-order those tests. So when they come in the office, as soon as they get in the office, they're swabbed immediately. And then I see them one after another. Because I've gotten the HPI, the history of present illness ahead of time, and I've already written it down, I don't have to sit there typing on my computer. I can go from room to room to room to room.

And during the pandemic, that allowed me to see about 12 to 14 patients an hour and still provide them top-notch care. Because I was able to go from room to room to room, examine patients, give them information and move on. And so it made me very efficient.

Now that we're seeing less sick during the summer, I'm more and more, while I am trying to call ahead of time and get that information, more and more I'm back to the old-fashioned way of doing things. Walking in the room, getting the history, writing it down, ordering the tests, examining them. But I still, when it's a busy sick hour, do try to call ahead of time to make my sick hours move more efficiently and see more patients in a shorter period of time.

So that's how my workflow has worked, how it changed during the pandemic, and it's slowly going back to where I was before, where I don't prescreen and get the history ahead of time. I get it in the office right then and there. But when I look at my schedule and I have an hour, let's say for sick hours, and I see there's already 10 kids, I know I can't do that in an hour without pre-screening. Then I do it.

When I look and there's only four or five, then I have a determination. If I'm busy, I don't do the pre-screening, I do it right then and there in the office. But it gives me the ability, like I said, be adaptable, be nimble. I can go either way and make sure that my sick hours run efficiently and I can see as many patients as thoroughly as possible in the timeframe allotted.

Daniel Williams:

What are those patient satisfaction scores, that patient feedback, been like for you over the last couple of years here with you implementing these new protocols and processes?

Dr. Dov Shapiro:

So as I mentioned, we normally run in the mid to high 80s, which I think is pretty good. And you're always getting people that are not satisfied about something. It's unfortunately for us, the complaints were usually one of two things. Either they were kept waiting, which we've tried so hard to fix. Or on occasion, they were upset with my front staff, which has resulted in some change to front end staff at times.

But since pandemic has started, we've actually been in the upper 90s consistently every single month we've tested. Last month was 97%. And that's because patients are thrilled that their kids can be seen the same day. I cannot tell you how shocked I was at how many practices during the pandemic stopped seeing sick kids. They tended to be practices that were owned by hospital systems.

Private practices tended to see sick kids, but at least here in Chicagoland, a lot of the major hospital systems, which actually own a lot of practices, absolutely, categorically refused to see sick patients during the pandemic. They shipped them all into their urgent care centers. They didn't even see their own doctor.

I was listening to a comedian on a cable channel the other day and he was talking about this issue. About, I called my doctor office to get seen and I was told, "I'm sorry, we don't see sick patients." And he was going on to make a joke. That's like saying, "I go to a restaurant and I'm hungry." "Sorry, we don't feed hungry people." Right?

Daniel Williams:

Wow.

Dr. Dov Shapiro:

So I was like, that doesn't make a whole lot of sense.

Daniel Williams:

No.

Dr. Dov Shapiro:

We see sick patients. That's what we're supposed to do and this has allowed me to do so.

Daniel Williams:

Okay. Thank you for sharing that. That is just remarkable. This is a good question. What is your opinion for RSV testing of adults between the ages of 21 to 64? Basically not the pediatric patients, not the geriatric patients, that in between geographic?

Dr. Dov Shapiro:

This is a little bit out of my expert range. Obviously I'm a pediatrician, but I'll tell you my opinion on that. If they are the parent of a small baby, I think it makes a lot of sense to protect their baby from themselves. If they don't have a small baby in the house, or they're not living with an elderly grandparent, I don't really see the utility.

It's like any viral testing. Nowadays with extended viral testing, we can find out if you have a rhinovirus, which is the common cold virus. Why do I need to know you have a rhinovirus? So you have a rhinovirus. RSV doesn't hurt 25-year olds. It just doesn't. Now, if that 25 year has a newborn baby, it's important to know. If that 25 year old lives with their 80-year-old grandparent, that's important to know.

Otherwise, in my opinion, I wouldn't be routinely testing RSV on people that age. I think that would be a waste of resources and unnecessary testing. Now of course there's going to be individual variations in some cases where that might be necessary. Someone with chronic lung disease, something like that. But for a general healthy patient in that middle age range, I don't think I personally would recommend testing.

Daniel Williams:

While we've got a couple of minutes here, I just wanted to get some final thoughts from you then. You have covered a lot of ground here today, a lot to absorb by our attendees. What are some final thoughts that you would like to share with them?

Dr. Dov Shapiro:

I think I said this out of my talk, but I want to reiterate it again, guys. I went into medicine to help people. That's what we're here for. The pandemic was very challenging to all of us and many doctors burned out trying to help people during the pandemic. Those that survived are the ones that had people backing them up and had the help. They had the support systems in place to help them through what was a very traumatic time in all of our lives. Worrying about our own families, about our own health, and our patients at the same time.

But also part of what keeps us going is the ability to do good. When we see we help someone, when we see that we change someone's life for the better, we go home. Look, we're not making widgets in a factory. We're not counting numbers and balance sheets for large corporations. God bless them. They're all necessary.

We spend our days helping people. And I've had hard days. We all have hard days. And I've come home and talked to my wife and she would say to me, and she's right, "Sounds like you had a really hard day. Did you help anyone today?" "Yeah, I actually helped two or three people that really needed my help." You know what? That feels good. We're privileged to work with people and make their lives a little better. And that gives me a lot of strength to keep going.

This system, I'm going to be straight with you guys. I got it because it was the best thing for my patients and for my practice. This system has helped me provide better care to my patients, provide better satisfaction, better clinical decision making. So for me, this is a no-brainer. For me, this was like, wow, I can be a better doctor if I have the system in my office.

It doesn't hurt that it also made my practice more efficient and made my practice more money and more financially sound. But I got into it for the right reason. I did it because I wanted to help my patients and it's done that better than any other system that I've come across.

Daniel Williams:

Okay. This has been a great presentation, Dr. Shapiro. There was one question that came in. Again, this may be not in your wheelhouse per se, but we want to get your opinion before we sign off. The attendee says, "As a follow-up to the RSV question for the adult population, how do you differentiate RSV from flu and COVID?"

Dr. Dov Shapiro:

That's a great question. So last year was very hard. This year we're hoping there'll be more seasonal, more seasonal predictability, but the way you differentiate, quite frankly is with a test. That's the beauty of Cepheid's multiplex test. It tests for flu A, flu B, RSV, and COVID, all with one swab. That's how you differentiate.

When do you differentiate? If the patient's really sick, if they're wheezing. RSV tends to cause what almost looks like a viral bronchitis or viral pneumonia. And children and elderly can get really sick and up in a hospital and on a ventilator. And people that are over 20, typically just a bad cold.

But if you walk in the office and you're wheezing and you're not an asthmatic, or if you sound like you might have a viral kind of process and you're worried about how that patient sounds, the only test I know of that can differentiate between those, other than sending a full viral panel for 100s of dollars off to a hospital lab, is a four-in-one one that's made by Cepheid. And that differentiates with one test, which one of the four they have.

By the way, sometimes they have both. In the middle of the tripledemic, I lost how many 100s of patients that had flu and RSV, that had COVID and RSV, that had COVID and flu. I even had one that had all three, the trifecta. But we saw a lot of that and this machine allows you to differentiate and find out what your patients actually have.

Daniel Williams:

Okay. Well, Dr. Shapiro, thank you so much. It's always so eyeopening and helpful to hear your presentation, so thank you.

Dr. Dov Shapiro:

You're welcome. Thank you. Thanks for inviting me.

Daniel Williams:

Yeah. Well, thank you everyone for attending. Those were some great questions. Thank you for driving this conversation.

The education for this session has now ended. Once again, we would like to thank Cepheid for their sponsorship today. Please visit their website at Cepheid.com/mgma, and there you can learn how their game-changing RT PCR platform can help your organization increase practice efficiencies, patient satisfaction, and revenues.

Now, if you do have content questions you didn't get answered, or just didn't think to ask today, direct those to Keil Brinster as Cepheid Marketing Manager at keil_brinster@cepheid.com. And if you have a webinar question, contact ed@mgma.com.

And if you haven't already, please be sure to click on the evaluation link. It's located in the learning management system. After completing the evaluation which is required to claim credit, please allow 24 hours for system communications to process credit for this session.

For more information on all of our conferences and webinars, please see the MGMA events page. Thanks everyone and look forward to seeing you at another online event soon. Take care.

Roy Oliveras:

Hello, my name is Roy Olivares. I'm a Senior Connectivity and Informatics Solutions executive with Cepheid. Today we'll be going over Cepheid C360's Turning Insights Into Action. I'll also be presenting with Mary Hammel. She's a laboratory manager at UCHealth in Colorado, and you'll hear a little bit more about Mary's story towards the end of the presentation.

Cepheid's three pillars of connectivity. Our Cepheid C360 team, we kind of cover a couple of facets of the business. The first being laboratory information management, meaning anything LIS, middleware, point of care directional, bidirectional interfacing. We also cover remote support, dealing with our remote desktop sharing file transfer. Then finally what we're here for today is C360, our streamlined support instrument and monitoring tool. So that's kind of what our presentation's going to be about today. We'll give you a little more information. We'll go through the slide deck. We'll go through a short demo so you'll get to see it in live action. Again, at the end you'll hear Mary Hammel with our customer story.

C360 is a web-based software. It's in dashboard format, it's in real time, and it gathers information from any GeneXpert system to enhance productivity and performance. How can Cepheid C360 help you? Real-time actionable data, so you'll be able to see trends, managing your instruments and monitoring their status, improving connectivity and reducing instrument downtime, sharing data with other instruments and institutions, fully customizing of thresholds, alerts, notifications, and then that remote surveillance piece we kind of mentioned earlier via the web for instruments and your disease state.

There's two dashboards today that we'll be talking about and you'll get to see them. First, the instrument monitoring reporting. That's going to be where you're going to track, you're going to optimize instrument performance, that type of stuff. Then the second part of it is going to be the disease state, the surveillance and reporting, and that's optional. But you'll be able to see a couple of disease monitoring solutions using this as your disease surveillance monitoring solution.

First off, we're going to go through instrument monitoring reporting. Real-time monitoring, like we mentioned earlier across multiple instruments helps with your instrument uptime. You'll be able to see if there's any kind of errors, support issues or anything with that instrument in C360. Then the other part of it is not only will you be able to see the instrument stuff, you'll be able to see how your testing is going for your performance surveillance, and then operators. You'll be able to see if there's any additional operators where you need to go back and do some additional training because maybe someone has a higher invalid rate than another person, so those type of things are involved in this instrument monitoring. It's not just the instrument, it's also including the tests and the operators.

What things are you going to see in there? You're going to see error codes, if modules are failed or disabled, instrument locations. You'll be able to see software versions. I know when you guys probably call into tech support, sometimes that's the first thing they ask. You don't have it right on you, so you'll be able to see serial numbers, software version numbers. You'll be able to see all of that stuff in C360. Then as far as the transparency of data, it's only instrument related service stuff, so successful, errors, stuff like that. There's not going to be any additional PHI or anything like that that's available in C360.

Let's take a closer look. We've got a few screenshots. Again, I mentioned I'm going to show you a live demo. I always like to show a few screenshots here. So tracking errors and invalids. You heard me mention earlier in the previous slide that you'll be able to see a few screenshots. The first screenshot you saw is related to the instrument, so we can break down errors by instrument. The second one, we can break it down by actual module so we can see individual modules to see if they have errors. Then finally we could take it a step further. We could actually see what types of errors are in that module. We could see if they're instrument related, test related, sample related, operator related. Really gives us a nice way of being able to see what types of error are we having, what can we do to fix those errors. Again, it's in real time, so we want to make sure that that data that we're seeing there is useful to us.

The second part of the dashboard is the medical and disease surveillance. We talked about the instrument, now let's talk about the disease surveillance piece. Again, real time you can see your usage. There's a cartridge utilization dashboard that you'll get to see where you'll see test and patient results. The two things it helps us with is the antimicrobial stewardship. So if you're looking at let's say MRSA or C. diff and you're trying to monitor your rates, you can get that real time and live on the GeneXpert. Most of the time you might have that data maybe in an LIS or in some other infection control thing, but it's maybe a week or 24 hours delayed or even a month before you see those reports. You could go and monitor this in real time and see that to help with your stewardship programs.

Then the second part is the epidemiological trends. You'll notice if you're covering a broad area, you have a large health system, you might be able to see a really quick way of mapping it because you're going to see on Google Maps it's going to have a spot and get a quick way of saying, "Oh, this person's higher than this person," or just be able to get a pattern recognition of your patient population.

One other thing that is really good for this too, you might notice, "Hey, I can see positivity rates. I can see other things that are going on with my system." You can also see if there's something out of the ordinary, meaning, "Hey, I looked at my site and it was only less than 5% last week, and this week's over 20. Why is it? Is it something because it's an actual positivity rate? Is it something that I need to address for contamination? Maybe someone got something that they shouldn't have done or they didn't follow the procedure of cleaning the area, and now I notice there's a spike in something," so you could easily catch that before it gets out of hand, which makes it really nice. There's nothing else that I have out there that can do that, have that capability.

Things that you're going to see in the disease surveillance, so again, trends, evolutions, positivity rates, any kind of resistance data. Types of data that you're going to see, so transparency of data, is only stuff that you want us to see. It's totally configurable by the administrator. So if you don't want us to see a sample ID or you want us to only see the actual data, stuff like that, you can configure that for you just to see and only for us to see positive and negative. So it makes [inaudible 00:06:28]. It leaves the choice of what you want Cepheid to see and support to see in your hands.

Let's show you a couple of screenshots of what that looks like. You'll notice here we're looking at the State of California medical dashboard, and then we can go down to the individual result. I can look at all of my trends for the data, again, I'll show you this in the presentation, or I can just look at one specific result. I can get those CT values without physically having to be in front of that instrument. That's the beauty of this. It's a web-based, cloud-based thing. I don't have to go to my instrument for data all the time. I can look it up from my office, from my home office, from other areas in the lab and get this information again, not having to physically be in front of the instrument.

Along with the data, we've mentioned that hey, you're sharing data, you're sharing the cloud, you're sharing this, you've got PHNPI. We want to make sure that data is secure for you so we have a nice security strategy. One, everything is encrypted. We have controlled access, and you'll be able to help us with that, meaning you'll be able to pick who the user is, the other users with it. We do use two factor authentication. Our systems are monitored 24/7 as far as segregation, and then we have US servers. Your data will be staying within the US, it's not leaving outside the US.

Then one little tidbit that I always like to point out is did you know TLS 1.2 is the same standard encryption level that banks use for transactions? Also, we're ISO 27001 certified. We've gone through all the security tests, we've done all of that piece of it, and we want to make sure that your data, whether you decide to send it to us or not, is monitored and secure. Again, you have the ability to configure what you're sending to us. So again, that data we keep as a security strategy with that.

Now, I'm going to stop sharing, and I'm going to go to my demo screen with it so you guys can see some of those demos because I know a few of those screenshots were a little fast. I want to show you what it looks like in real time. Now, we showed you the presentation, we showed you the screenshots, and like I mentioned, we're going to give you a little bit more in-depth demo.

The one piece you didn't see was me logging in and getting the two factor authentication, and the reason is is because you have to wait for the passcode. So you log in, it sends you a passcode like most things do to your phone, you type in that passcode, then allows you to log in. It's just for security purposes. We want to make sure the person logging in is the person that should be logging in, in case you ever lose anything like that.

What you're seeing here, let me orient you to the screen, is first we have what you want to look at. So we've got medical dashboards, like I mentioned in the presentation. We have instrument dashboards, we have test results and notifications. This is what you want to look at, and then this is what assays do you want to look at and what do you want to specifically look at. I have SARS checked for here and I have positivity rate.

You could pick whatever assay you're looking at. So let's say you, your lab did strep or you did C. diff or you did MRSA or you did chlamydia, gonorrhea. You could go through the assay window and check exactly which one you wanted to use and then you could see exactly what you wanted to see on it. If you wanted to see positivity rate, negativity rate, those type of things. Then you could pick your date range. We have kind of some default ones here: this year, last year, three months, or you can put a specific date range. Then finally, once you fill in what medical dashboard you want to look at and then what you want to look at, you'll come in here, and you'll see where you want to look at it.

Obviously you're not going to see the whole US. This is for the demo site. You're going to see your individual sites here. The nice thing about it is you'll be able to pick your site. First thing you're going to see, depending on what you picked, is your positivity rate. You'll see a trend line. You can pick it by month, week, count, however you would like to look at data and you can have your raw data down here looking at that.

This is kind of the view that everybody uses here. This is one that most health systems, I think even Mary might use this view, is you click the map view. The map view is super helpful. It's basically a snapshot of what you're looking at. In California, me as a customer, I have three cities and I have three labs. If I was a health system, I could go and see how each one of those are doing. I could click on it. It would tell me my positivity, my negativity rate, that type of thing just as a snapshot, me not having to physically go look at the trends, but I could just go in here, and I could see exactly who's doing well and who's not. This is amazing for health systems, especially if you're across a whole state spread out like you're going to hear from Mary shortly. You can just go get that snapshot or even mentioning in the disease surveillance, if you see something really weird, you can find it out here. Why did they go from five to 25%? What's going on there? Nice little snapshot of that here.

This is again, the medical dashboards. Obviously there's more that you can get into. We could go into a whole day of doing the training on just how you use C360, but I wanted to point out the trend line, how you find your stuff and then the map and the data grid. There's also test results, so you can individually see a test, and you can click in here. You can see system name, software version, lot numbers, CT values, all of that information here per each test. Again, I mentioned it was totally configurable by the customer, but if you wanted to see sample ID, it will show up here as a sample ID, so you'll be able to see that and do some of that information. Again, that's on your end to decide if you guys want to give us a sample ID or not. But this is all the basic information of users and logins. Again, having this at your fingertips without physically having to be in front of that instrument.

The next dashboard I'm going to show you ... So that was the medical dashboard, again, going over positivity, negativity, seeing the trends, seeing the maps ... The next one is the instrument dashboard. You'll see all your connected instruments here. You'll be able to go into that individual instrument. You'll be able to see the serial number of the model, what version of software it's on, when you communicated last. So if you're having issues with LIS dropping communications and stuff like that, if your LIS is probably dropping communications, this is probably dropping communication too. So you'll be able to go in here and see what was last sync time, when the QC was last started, those type of things.

Then you'll be able to go and break it down by individual module number here. You'll be able to see your percentages here. So you can see I've got about 11%, 9%, and let's say, "Hey, I want to take it a step further. I want to see what types of errors are this 9.5%." I can click in here, and I can get that information. I can see that they're all kind of across the board. I see sample related errors, instrument related errors, those type of things within that particular module. It'll be able to see, does support need to get involved? Do I need to call support?

Then if you did call support, you'd be able to give them a little bit more information, not just, "Here's my serial number. Here's what I'm seeing." You'll be able to give error codes. You'd be able to give stuff that they'd be able to start troubleshooting and getting back to you faster and maybe cutting down on some of that back and forth between customer and tech support. Also, some of this data is already in C360, so they'll be able to use the C360 data to troubleshoot.

Again, I'm going to say big thing, it doesn't fix all, but it does fix most. So you might have to physically send a file in here or there, but a lot of the files that they need to get the case started are in C360. That was instruments and going into the individual modules and stuff like that. Let's go to test results now.

Test results is kind of a mix of the instrument dashboard and the medical dashboard because it gives us successful, unsuccessful rates. It also gives us the cartridge utilization, which is really nice. You could kind of see is one instrument doing more than the other, those type of things. You can kind of see your peak time. So it's really nice if you've got PM schedule to go in here and go, "Okay, my down times are usually between 5:00 and 6:00 in the morning," or, "In the afternoon later, we don't run quite as many, so we know when we schedule a PM we're either going to do early morning or later in the afternoon." You can see exactly about how many you run on average. Makes it really nice. Nobody wants to do PMs between 9:00 and 12:00 because that seems like it's the busiest time for the lab.

You'll be able to see here error rates, stuff like that. The nice thing about the error rates, you can click in here. You'll get a little bit of a description on here and a code for the error rates in your no results. The other nice thing you can do here in test results, as you'll notice there's this little advance and there's this export file. You'll see the export file a few times around the demo software. Anywhere you see that file, you'll be able to download that information to a CSB. So basically pulling this data into a CSB so you could do an Excel workbook, anything like that.

But the reason I wanted to show you this is here this little blue kind of dot. You can go in here, and you could pick test type. So if you wanted to make a QC report with this data that's being run, you could make a quality control report, you could make a specimen report, you could look at both quality control and specimens in here. You notice that kind of changed up when I clicked that, but you can do the filters, you can click here and just do it by one laboratory. So if you wanted to create a QC report for one specific lab, you could go in here and do it for a specific serial number, which makes it really nice. Probably currently you've got a clipboard that you write down all your information at the end of the month or the end of the week that QC is done. We can automate that process, and you can print this out in a nice report either at the end of the month or end of your quarter, stuff like that. Very nice again, in this QC test result here and exporting those files.

The last one is notifications. I don't have any notifications set up, but I wanted to mention this. You could set up notifications for assays. So let's say you want a notification when SARS gets over 10% positive or C. diff is over 10% positive or something like that. You can click here, make a notification that you'll get an email when that's 10% positive over seven days, and it'll keep sending you a notification until you turn it off. Basically [inaudible 00:17:00] you, "Hey, come look at C360 because I'm seeing a higher positivity rate that you normally don't see, and I'm sending you a notification to tell you that."

The other administration things are more for you when you set up stuff. Users. Just want to mention one thing. There's a couple of types of users. So it's nice that it's configurable to you. You can give people admin rights, you can give them just general lab user rights, you can give them epidemiology rights, meaning they've got a view-only mode in there where they could see that and not do a whole lot with it. But it allows you to be able to share this tool with other parts of the lab, basically getting outside the lab. If you wanted to share it with infection control, if you wanted to share it with other lab members, team leads, stewardship program leads, you could share that with them without them having to look at, "Hey, you guys have this error rate or this." They could just see the positivity, negativity disease surveillance. So it's very nice for you to be able to share those different parts of the actual hospital with C360.

Then finally you'll notice an audit trail, and the audit trail's just for if you wanted to keep track of who's logging in, when do they log in, those type of things. It's more for security purposes. Everybody wants to know what's going on and doing, especially if you get a bunch of different users and you want to make sure not somebody's logging in there all the time or they're pulling data that they shouldn't be pulling, you'll be able to go back to that audit trail.

With that, I'm going to go back to the slides and tell you a little bit, "Well, you've told me all this great stuff, Roy, about how it does this, this and this. How do I get it?" I want to go over that piece here. So I'm going to switch back over to the slide deck if you'll give me a minute or so and then turn off the demo site.

Again, you've heard the presentation, you've seen the demo. How would you actually get this? What would be the implementation process of C360? First would be a signed C360 user agreement. This can work two ways. One, you can already have it maybe in your placement agreement, your service contract, that type of thing. Or you can individually sign a C360 user agreement with one of your connectivity and solutions executives. If you want to find out how, if you do have it in your contract or if you have a valid one, you can always reach out to your sales rep. Ask them if you have it. If not, you can reach out to your local connectivity and solutions executive for your area. They'll be able to tell you, yes, you have a valid one or it's included with your contract, and we can sign you up for C360.

Once we do that, you've got a valid contract and everything, we want to register your account. We'll come to you for a little bit of information, maybe some addresses and stuff so we could do that mapping on the Google Maps, especially if you've got a large health system, and you're going to have across the state or across the city type of thing. We'll want to get those maps and have it accurate.

Then next we're going to set up the data collection policy on your terms, meaning what you tell us that you want us to see and want us to share, that's how we'll do it. So we've got a couple of little check boxes that you'll tell us, "Hey, I want you to see this," or, "I don't want sample ID," or, "Yes, I want sample ID." Then finally we'll help you set up those initial user accounts, basically sending you invites to get users set up. Then after that we'll show you how to set up other additional users. So again, if you want to give other people outside of the lab access to C360, maybe in pharmacy, the stewardship, infection control, you'll be able to set those up for them. We just set you up with that initial one.

Then finally, what do we have to do to get all of them talking from the GeneXpert to C360? Once we set up an account, we have a registration code that's unique to your site. We will install an application. It's called C360 Sync. Sometimes it's already installed on your computer, and you don't have to do anything, but what we'll do is we'll get that application installed if it's not on there. We'll type in or enter in that registration code, and that unique code will then connect your instrument to your account in C360.

So now, Cepheid C360, in a nutshell, it's a web portal. It aggregates in that dashboard format. It's real time. You've got the two dashboards, the instrument monitoring, the clinical surveillance. One thing that I have not mentioned yet, it's included with the GeneXpert solution, so there's no additional cost to use C360. It's included as a part of your software package. We improved the support and the security. The only two prerequisites for C360 is the internet connection, so we have to have an internet or network connection. Then finally that agreement. Again, you could either sign an individual user agreement or it might already be included in your contract.

Then also, I always like to mention this at the end, it's a living solution. We're constantly making enhancements to ensure either the security level's up for any other kind of things that are out there. Then if you say, "Hey, I like this dashboard, but I wish it would do this," give us that feedback. We'd like to be able to make it more user-friendly. We want to make stuff that is able for you to use and see the data how you would like to see it.

With that, I've been teasing it all day, but we're going to hear our UCHealth connectivity story with Mary Hammel. Mary Hammel is a Laboratory Manager with UCHealth in Colorado. In this role she's a Best Practice Team Leader. She sets strategic directions for point of care programs at 12 hospitals, 12 freestanding EDs, and 145 urgent cares and primary care clinics for UCHealth. I know this is changing all the time, she's always adding on and doing a bunch of different things. Mary's been a laboratory scientist for over 18 years. She's got background in microbiology, molecular diagnostics before moving into that point of care realm.

Then finally, I always like to say Mary's quote for C360 because it's great. It really impacts probably what you're thinking about out there. She's like, "Learning how to fully utilize C360 has really provided us with confidence that our instruments are functioning properly at all times, and it gives us the ability to monitor positivity easily. It has really cut down on all the visits to our clinic." So with that, I want to introduce Mary Hammel. She's got one more slide here just to talk to, and then she's going to go over how C360 has been for them. What things that they've learned, what things that they've helped them with, those type of things.

Mary Hammel:

Thank you, Roy. When UCHealth began our journey with Cepheid, I'm not sure that we knew how much we would use C360. In fact, I'm not sure that initially we turned it on. We have quite a robust IT system, and as Roy mentioned, there are security requirements. I honestly thought it would be, because my IT system is pretty tough, I thought it was going to be a while before they would clear our security. Actually, because their security system is so tight and up-to-date with all of my IT department's requirements, it actually went through really easily and pretty quick.

The first two things that I really wanted out of C360 that it gave me were the remote monitoring. You can see with all of these clinics, I had a team of three, three people, one in each region, so basically a North Colorado region, a Metro Denver region, and a South Colorado region. Most of these clinics, with the exception of the freestanding EDs, they're all waived. So it's not like places we have to visit all the time. But it had to be easily installed, something that we could monitor all of the machines remotely and see what was going on so we didn't have to actually physically go to each clinic to see what was happening.

This software was great for that. We can monitor the modules, we can monitor the machines, we can make sure that everything's working. We can look at the errors, whether there was not detected or whether it was an operator error, whether it was an internal control error. Along with controls, we can monitor all of the quality control that the users were doing. We also were using quality control as a training piece so we could also watch that for the operators and make sure that they were doing that.

One of the things that I also really wanted to make sure that we had, because of my background in molecular and as a laboratory scientist, I honestly never thought that we'd be putting PCR in point of care settings. So when I was doing PCR before, long time ago, we were always worried about contamination, and that was one of my personal biggest fears about putting PCR into clinics was contamination. I wanted to make sure that I could see that immediately so if I saw clinic's positivity rate go up for no reason, I wanted to be able to jump on that quickly. Can I see that? Yes. Has it ever happened? Not once. Not once since we've gone live have I had any kind of contamination issues. So that's a relief to me, but I know that a lot of people want to look at that and have concerns about that because of our backgrounds in microbiology and molecular diagnostics. Hasn't happened at all, but you can still watch it like you'd want to.

The other thing that was surprising that we had not intended initially is that we moved from antigen testing to molecular testing 100%, so for strep, flu, RSV and COVID. We don't have any antigen testing, but prior to putting in Cepheid's, everything was antigen. We had no ability to see flu in the community or RSV in the community until they came to the hospital or were hospitalized. As a microbiologist, we always used to ask ourselves, "Who's going to have the first hospitalized flu patient?" That for us always signaled the beginning of flu season. But now, now I can see all of the clinics. I know when flu is in the community now. I know when RSV is in the community because I can see it. They're not hospitalized, they're not sick enough to come to the hospital yet, but we can watch that ramp up, and we never had that visibility before. So that was a surprising benefit of C360.

Then like Roy said, that they're a living solution. This really is true. We have brought to Cepheid a couple of ideas we had for enhancements, and we're also working with them on a pilot where they're helping us monitor our instruments. There have been more than one occasion where they have actually told us, "Hey, you know what? You've got a module that is not functioning properly? We're going to send FSE out to replace that module for you," before my team even knew or had gotten the phone call from that clinic that there was something wrong. We love the ability to help Cepheid kind of tweak the program for everybody and to find new ways to make things work.

Roy Oliveras:

Thank you, Mary, for that. Now we're going to go to a live Q&A here. So if anyone has any questions or you've been thinking of anything or you've typed something in the chat, now's the time. We'll break out for a live question and answer session. Thank you, Mary.

One thing I want to add was the pilot program that we had with Mary, we're hoping to take that out to a bunch of other different health systems. Right now we wanted to do our learning piece with Mary. So Mary was very graceful to be able to allow us to learn and get procedures in place in how the stuff [inaudible 00:28:44] going. So hopefully in the future we'll be able to pass that along to everyone.