This module we're going to be looking at laboratory testing applications to chronic diseases and we're going to start by looking at what chronic disease programs exist in public health and how they work. So the leading causes of death in the United States are mostly due to chronic diseases. They include things like heart disease stroke cancer diabetes obesity and arthritis. They're among the most common and costly diseases but they're also preventable. As of two thousand and twelve the last year we have data for there is one hundred seventeen million people who have one or more chronic diseases these are not limited to elderly people we are finding that more and more young people have chronic diseases like diabetes that usually would occur in people in their fifty's and sixty's but now we're seeing these occur in children who are even as young as three or four. Diabetes is particularly important because overall in our country we see about twenty five percent of adults who are obese obesity is a major risk factor for developing diabetes children so in some states that rate can be even higher for example here in Michigan being one of the heaviest States over a third of our adult population is obese. And in children aged one to two to nineteen year olds there are about one in five or twenty percent who are now obese. Arthritis is a common cause of disability this makes people on able to work and in peers many of their basic functions of life. Diabetes is also. Related to developing kidney failure which is a another cause of disease chronic diseases. So in addition to being an actual cause of death by itself it leads to other leading causes of death like diabetes we also see a high rate of amputation in people with uncontrolled diabetes who have been diabetic for many years. Many of these causes of chronic diseases are interrelated for example heart disease and stroke are related to related to each other diabetes and heart disease are related so none of these are easily teased apart often the underlying causes can be identified as being overweight smoking and smoking and these then lead to many other of these leading causes of death. What public health does about chronic disease is that there are programs at the state local and federal level that have these functions first of all they're responsible for surveillance that would include monitoring the number of people and the characteristics of the population with different chronic diseases. Public health programs participate and fund transistor transit translational research translational research is applied research where you're taking some basic knowledge and then applying it to a real every day problem an example of that might be a gene that is an underlying cause of diabetes and so now you're going to we've identified that gene and now we're going to use said in a study in which we look at knowing if the population who knows that they have that gene does that change their approach to their lifestyle in such a way that it has a positive effect. John there outcome so we know so the basic researchers find out that there's a gene that's related to this chronic disease problem the translational research or is going to determine if knowing that or using that basic knowledge from the laboratory is going to help our outcomes. They're also a really they are responsible and are very much participating in health communications and because these diseases occur at a population basis they're very widespread they in they occur in many different populations but also subpopulations So there have to be messages that are available to the masses about preventing chronic diseases and they have to be relevant to the population that they're targeting for example if you're going to target young people using Internet advertising might be more appropriate than if you're targeting people in their seventy's and eighty's and maybe newspaper ads are more relevant to that population just because that's where they go to get their news whereas young people go to the Internet to get their news. Policy Development is an important part of chronic diseases so some examples of successful policies have been the high taxation on cigarettes and other tobacco products another. Which the result of that has been that it makes it buying cigarettes more inaccessible to young people another example of a cesspool health policy that has addressed chronic diseases the indoor ban on smoking this has led to fewer exposures to secondary smoke and also it also it be as it becomes increasingly difficult to smoke it'll make people less willing to continue to smoke if they've already started. But there's a lot of policies that still need to be addressed for example our food Polly. Sees a nutrition obviously obesity is a major cause that underlies these chronic diseases and we have to find policies that are going to promote healthy eating and healthy lifestyles as opposed to policies that promote unhealthy eating. The public health chronic disease programs also focus and accomplish all these task lists it above with partners they engage their partners and they work toward mutual goals for example the American Cancer Society made to receive funding from a public health program to develop a health communications or a they may work together to do research. It's also important that the public health programs in chronic disease work closely with the medical community because he you receive the care for these chronic diseases in the MET in the medical setting it's important that they're also engaged aware of the most current research and treatment options one thing you'll notice about all these functions of chronic disease program is direct care is nowhere here so we don't have chronic disease clinics set up in public health we will have lifestyle clinics set up in public health or we may public health programs me assistance screening and directing people into appropriate care or encouraging them to make lifestyle changes but we don't do direct hear her say. Some of the various programs that are included in the purview of Pope Paul public health program cracking diseases include cancer these programs may focus on cervical breast cancer. Awareness so people are get women are getting screened. I and the appropriate screening will work with funders too and funders to make sure that people have access to screening options like mammograms and are aware of how they can take care of their own screening as well as of things that they can do for their health to prevent we also have registries of cancer These would include information about the tumor itself as well as the demographics and risk factors associated with different cancers this is a very rich source of data for researchers who are doing both basic and translational research Public Health has the authority to mandate that these are reported in the same way that they have the authority to report that communicable diseases are reported. Chronic disease programs also focus on diabetes and Albion talking in more detail about how the laboratories involved in that asthma programs will develop screening and Prevention practices referred to have health would include family planning programs these are often located either in chronic disease programs but they are may also be included in maternal child health heart disease and stroke as you can tell from the leading causes of death are major read major causes of death in the United States one particular program that is funded federally and implemented on a state local level is the wise woman program in this exemplifies many of the. Characteristics of public health program these are provide resources for women financial resources for women who are below poverty level to access screening for a variety of chronic diseases including blood pressure monitoring and cholesterol testing. They can also offer testing for diabetes and the women who are identified at risk are not just referred to a medical home but also they are giving additional lifestyle coaching like how to cook nutritious meals and how to exercise in your every day life like how to take walks include walking into your every day. Every day routine. They get assistance with quitting smoking through Access seeing quit lines and non smoking classes and the interventions may change from different programs from state to state or from jurisdiction from jurisdiction but they're all I have the common will of provide loading healthy lifestyles and women who have been identified as being at high risk. Wellness programs include things like nutrition public health nutrition it would going to have an entire module on this particular topic activity and exercise a tobacco use and here the focus is on developing policies that make it more difficult to continue to use tobacco as well as to bring awareness to the individual a how to back zero is harming their health. Substance Abuse and Mental Health again are very interrelated and they often may be standalone programs or they may be included in wellness programs that are part of chronic diseases workplace health promotions are programs that are generally administered at the local level which will go into work sites and provide testing screening for high cholesterol glucose in order to identify employees who have and also take their weight and calculate their. B.M.I. in order to identify people who are at high risk for chronic diseases and then they are directed into medical care but often the employer then also offered other programs like Weight Watchers on site and encouraging Joakim during the lunch break and programs like that so public health sort of is the impetus for the spark that lights the prevention fire at a particular workplace. Oral Health would include. Private programs which are geared toward book prevent dental diseases so they may include screen and dental care but they would also be. Promotional messages health promotion messages on how to keep your mouth teeth and gums healthy arthritis programs are going to focus on how to prevent arthritis and the way we look at prevention in these public health programs focusing on chronic diseases is on three different levels the primary prevention is to make behavioral changes through education and health promotion that will prevent the chronic disease from ever occurring so if you can get children to eat healthy and exercise they will become obese and then they won't be adult obese teenagers and young adults who are at high risk for chronic diseases so this intervention happens early they have to be based on evidence in order to be successful so you need to know where the at risk populations are what the successful programs are and also. Who they are who are getting this the disease that you want to do an intervention on and the case definitions again are largely going to be based on laboratory data so this is what a way in which the laboratory is involved. In chronic diseases as in formulating case definitions that are then used for research that feeds into primary prevention secondary prevention is early detection so these will include screening tests and diagnostic tests so screen test are identifying people who are at risk diagnostic tests are identifying people who actually have the disease so in public health the role of the laboratory is to identify appropriate tests that have the right characteristics to use for screening and also those that are appropriate to use as diagnostic tests so even for the same intervention like lowering cholesterol the same test for screening and the test for diagnosis can have very different test methods as well as test performance characteristics it's because again remember that with a screen test we can tolerate a high level of false positives. If we have a good confirmatory or diagnostic test that will give us that specificity so we go for maximum sensitivity in a screening test and maximum specificity and they confirm atory or diagnostic test. It has tertiary prevention includes those activities that public health will encourage for people who are already develop the disease and now the focus is in minimizing the effect of the disease so in diabetics it's going to be helping them stay on their their eating in activity routines it will be for measuring and here it's so that is where the laboratory gets in involved in these programs what are the best Beth methods that we can objective Lee use to monitor it here it's so we can use it into. Diabetes you're familiar with glucose monitors that's one way in which we do that that monitoring but there's also other ways for example I heard of a very innovative program that's occurring in Oregon and which the local health department is partnering with the health system to to address smoking in pregnant women and they're using the laboratory test which is a marker for second hand and primary smoke if this is a metabolite of nicotine called coltan in and the laboratory is measuring cotinine in these women if the women are successful in quitting smoking through all the support that these programs provide they get a financial bonus when they deliver the baby and in this way the public health program and the health system hoped to avoid those high costs and bad outcomes associated with low birth weight and low birth weights are associated with smoking during pregnancy. We're going to focus on one particular disease chronic disease type two diabetes and just to. Review what this is this is a disease of fat in carbohydrate metabolism abnormalities the pink Riyad of beta cells their job is to produce insulin in type two diabetes they start to dysfunction and they don't they don't produce as much insulin. Additionally the muscles cells liver in adipose tissue all develop insulin insense insensitivity which means that they can't respond to insulin as an usher they can't take an insulin with glucose into the cell so we have this dysfunction of not having enough insulin and what insulin we do have. Can't Usher glucose into the cells where they need to be used. The symptoms include thirst blurred vision and weight loss the complications of to diabetes are related to the the tissues that there's high glucose circulating because it can't be assured into cells it damages blood vessels in the heart and this can result in heart disease if our stroke if those small blood vessels are in the eyes we start to see loss of vision and blindness those small tissue those at Andal feel cells lining the vessels of the kidney when they're damaged because these high levels of glucose they result in kidney failure. The small capillaries and that feed the lower extremities when they start to get very rigid by having pounced in exposure to high glucose they start to lose function in when tissue can't doesn't get blood to it because their blood vessels are damaged you start to see necrosis and dying off of those cells of all but eventually those are going to be so much tissue that is necros to that it's going to warrant Taishan. Neuropathy occurs because again these glucose high levels nerve tissues get damaged also by lack of blood flow as well as by the glucose so you see without lack of it with that neuropathy diabetics have problems with Di diarrhea and also with loss of function in loss of feeling in their feet they don't know when they've been injured and then the injuries become rampant Lee They because of all low blood flow to that that injury the body can't fight off the infection very well and it results again in amputate. Paradoxal disease these are diseases of the gum in which this is a both a cause and an effect paradoxal disease is related to developing diabetes and also periodontal disease it has bad outcome for someone who is already diabetic one of the ways in which that happens is that bad the inflammation the chronic inflammation that occurs in the gums during periodontal disease brings all kinds of antigens into the blood that are that again cause a widespread inflammation and one of the things that inflammation will result in if it's chronic is more damage to endothelial cells lining all these organs that I've already identified a reptile dysfunction occurs and male diabetics again because of the lack of blood flow to the to the **** and we also see in association with depression this is related to Sara Tonin levels and the ability of the brain and other tissues to produce their atone and and prevent depression from occurring. Diabetes is managed by weight loss diet and exercise and someone with AIDS actual diagnosis of diabetes through these things if they're very successful can become non diabetic if though they can't manage the diabetes through weight loss diet and exercise we start to use medications and these include insulin and or moral oral medication and these then serve as the replacement for one or more of those path ologies So if your cells yourselves or your pancreas can't make enough insulin this is going to be an artificial replacement if your cells are not your insulin your cells are insulin. Resistant and they're not taking in the insulin the medications can help bring the glucose to the cells and again monitoring of the blood glucose is very important to determine if the patient is in fact successful in keeping their glucose levels down and avoiding these path ologies from occurring. A high level of glucose in the blood is referred to as glycemia a very low level hyperglycemia a very low level of glucose in the blood is hypoglycemia. So who becomes diabetic the risk factors include age the older you are the higher your risk for diabetes race is also related to developing and we see this occurring more in. And both race and ethnicities we see this occurring in. African-Americans at a higher rate than Caucasians and we also see it occurring in. Hispanic populations as opposed to non Hispanic populations and we see very high levels in Native American populations family history is very important family history is important because not only does your family mold the way you eat and your lifestyle in terms of what you enjoy doing and how you spend your time so if you come from a family who likes to watch T.V. together and do sedentary activities you're more likely to be a person that enjoys those activities throughout your life if your family is active you're more likely to be active We also learn a lot about eating and what we like from our family and if a family tradition is to get together and have really big really high fat meals that will be a true. Mission very poor for your health but it will be a tradition that you carry throughout the rest of your life. So take those things together and you can boil them down to the result of obesity and inactivity and those are the reasons why we see. That will lead to these are the underlying causes that will lead to to die of type two diabetes having had just Station diabetes is also a risk factor so during. The just ational preparing a pregnant women are monitored closely for their glucose levels because this is more likely to occur during that time period after the pregnancy is over women will generally revert back to a non-diabetic state as they get their weight under control but ever having had gestational diabetes even if it's been twenty years ago again will be a risk factor. And then again then we see this associated with poverty poverty is not an underlying cause but it's an association of people who are poor don't have access to healthy foods is readily they don't have grocery stores perhaps in their within walking distance and they don't have transportation to get to grocery stores that have healthy food options so they have to. Shop at convenience stores and the candy and stores are going to stock things that they can keep on their cells for a long time which tend to be highly processed foods very high in fat and very high in sugar as well as preservatives. So the bottom line is is that in the United States we are witnessing a diet a type two diabetes. Epidemic And again it's not just in older people although as you get older your risk increases. But we're also starting to see Type two diabetes in children children as young as three and four and it's going to. As those as the population ages and the chronic effects of diabetes continue to develop we're going to see a higher cost in terms of amputation and kidney failure. So let's now look at the laboratory science behind monitoring glycemia or blood glucose. We measure glucose in the laboratory as an indicator You'll recall that I said that we might measure a substrate we might measure and the enzyme or we might measure the product in the case of glucose of diabetes management we're looking at glucose we're looking at glucose because it's relatively easy to measure and it's highly predictive of pathology so it's a very good. Biomarker to indicate what's going on in terms of a diabetic status so it is the substrate the enzyme is a glucose oxidase in the body it would be a different enzyme that is breaking it down to turn it into energy in the laboratory we use glucose oxidase. Which is an enzyme that in the presence of peroxide and oxygen is going to take our substrate and our product is going to be glue cure on an acid in hydrogen peroxide now we can't again while we can't see our measure the amount of glucose easily with a laboratory instrument we also can't measure glucose and to conduct acid easily so we're going to. Invert these products into something that can be measured readily and we take this a secondary product hydrogen peroxide and when it's mixed with a colorless dye. In this case Diana saw die die and side. It's going to end the presence of an enzyme a second and Sun peroxide days is going to turn these this and brown because we're going to get water and we're going to lose electrons and oxidize this. This and die and it's going to become brown Now this is fairly in stable so we're going to then reacted with. Another chemical and then we're going to get a stable colored product the concentration of this colored product is going to pinpoint a portion all to the glucose that we started with OK so we can measure this with a spectral photometer or other mechanisms that we use in different laboratory instruments it may not be a color reaction it may be measuring the electrons that are being passed here but we're going to be looking at a relationship between the glucose and either a color or an electrical current. So this is the chemical reaction for glucose we also have a very powerful tool in the laboratory that we measure the level of. It's called A one C. quite costly to hemoglobin hemoglobin becomes how can grab onto glucose if it's for floating around in the serum or plasma It does this because it's a sort of a temporary storage for glucose after a meal your. Everybody diabetic and non-diabetic is going to get a big rush of glucose in their cells and your insulin can't mant can't take it into cells where it's needed and it can't convert it your body can't convert it to fat quick enough so as a temporary holding we're going to hold on to it with a hemoglobin molecules so if you have a chronic high hyperglycemia your. Hemoglobin is going to be more likely to be holding on to blue coats because it's been shoved off there in times between meals when your glucose level starts to drop you can release those so even if you're temporarily have a high. Rated hemoglobin later in the day several hours later it became a global will start to release that in equilibrium and the in the glucose then becomes available in the plasma and can be ushered into cells with insulin. For Use immediate use so it's sort of a temporary holding pattern people who have a chronic hyperglycemia will also have a chronic A one high A one C. The reason that it's even better than glucose as a monitoring. Monitoring tool is that glucose is a variable so you can. Be very diligent about your diet for a day or two before you're tested and it will look like your glucose is in control however you're A one C. is more of a long history of what's been going on with glucose in your body for a longer period of time. The American Diabetic Association recommends that diagnosis of diabetes is done with a A one C. measurement or. A fasting glucose done in a laboratory and I'm going to show you why these home glucose monitors are not F.D.A. approved nor are they should they be used for diabetes diagnosis. OK Another way of diagnosing diabetes is to have the patient fast than give them a dose of a known amount blue coasts and then the then if the glucose is very high in the blood it means that the insulin is not available and it's not being utilized. So we can look at a long term Luko status or a controlled glucose dose or even a fasting and these are relevant for these are relevant for. Diagnosis OK And I want you to note also that the American Diabetes Association recommends that these are done in a standardized and that the results are standardized that they're not done just on these glucose monitors but they must be sent to a laboratory and I'm new to show you why that's very important the blood samples for in providers offices are not standardized for diagnosing diabetes OK They're standardized for monitoring in individual's patient status from hour to hour and from day to day but they are not interchangeable. And what we recommend are what they Merican Diabetes Association recommends is that the the patient a diabetic patient uses a blue blood glucose monitor at a minimum to measure their glucose in the morning and before meals and then adjust their insulin dose based on that if it's high and they're going to eat they're going to need more insulin if it's a low cut back on the. Insulin or take in more glucose They also a recommend that A one C. is measured three to four times per year and this again is giving you a long term picture about how well that diabetes suspend measured. Has been controlled. So why aren't home glucose monitor suitable for diagnosis Let's go back to the calibration curve and you'll recall that we have a concentration of R. and A light and we have absorbance on the Y. axis and we plot the standardized we have a standard and we know that it has X. amount of an a light and we and when we measure the absorbance after the chemical reaction we put a point on the line and then after several standards at different concentrations are plotted we draw the best line through here when we measure the patient serum this unknown amount of an ally and we get a. Sense we can then use this calibration curve to determine what the concentration was this is in a perfect world in a perfect world remember a group the perfect calibration curve is going to be straight it's going to go through the origin it's going to. Cover all relevant values in that biologically relevant values the entire range what we might see in people both people that are diseased and normal. But we don't have a perfect world what we have is we usually have to use a regression analysis to draw the best flying that we can and even when we draw the best line that we possibly can we're still going to find that we have data points that lay outside away from that line OK. So. This line is linear and it's also by variance so we have two different variables that we're measuring here the formula that defines this lion is why equal eight zero over in a one so a zero is the Y. intercept and a one is the slope the formula for the line then is why equal a zero point one. So if we want to measure how good this line is we're also going to look at how far our data points are from the line and we do that with a process called the standard error so we're going to take the distance here from our drawn the line long drawn by regression and measure this distance and you can see these lines here indicating how far we are from the line this is a really good line and that our data points are all over the place they might be appear they might be down here this is a pretty good line here that we have. So the standard error is the average distance from all the data points. That Fought for the that fall for the IS c average distance that all data points fall from that line so we measure the distance each data point falls from the line and then take the average. OK And that's defined by the difference between wise. OK this is going to give us a able to use a calculation called the R. squared the R. squared is that standard error over the average error. That is subtract that that product is subtracted from one and then. It's given us in our square a perfect line is going to have in our square of one a very low Our Square is going to indicate that our data does our line does not represent our data very well it might be the best line based on what we have but it's not a very good lying so in the example that I showed you earlier we had a really good line we had an R. squared of ninety nine but we lost fit at both high and low values so let's go back and look at that and I'll show you what I mean by that. OK So up here at the high values you can see that there was a an error occurring here and here moves. I Here in here you can see the distance from the line and then down here also we were losing we were losing it we were losing we were increasing our error and losing our accuracy because our values now are off the line here in the middle range though we had really good data points in terms of the rigor line that we grew the regression line so that's what's happening when we measure these glucose values what we see is that you can choose to lie in that captures the high values very well or you can choose a line that captures the flow very lines very well but very few **** A's can capture both the high and the low. Values the F C F C's that can capture both the low in the high are the ones that are more difficult to conduct and require more sophisticated equipment so they're the ones that are done in the laboratory and that's why the American Diabetes Association says based diagnosis on a laboratory method that standardized. So. Let's look at how that might be how that might work so if we're. A manufacturer of a look host monitoring device and we have these data points the regression analysis would tell us that the best flying is the red one OK that's the one we already get true but if your intent is to measure the data points at really low level she might choose then the green line and get better representation at the lower levels but then sacrifice. Accuracy at your high levels alternately you might be more interested in the high levels and less interested in low levels and you would choose a different line but when we then measure our patient on these three different instruments that we've we've gotten three different. We take the same specimen from a patient and measure it on these three different regression lines when we come down to our concentration you can see that we're going to get variability OK and it's not a matter of this of this test be necessarily wrong but it's not intended for that use OK in high levels we're going to see in some lines it's going to be if you chose for the low level she going to have value closer to the actual level in if you chose the line for it with the high values your result is going to be closer to the. The high of the target high value and if in so the one that chose the low values then they're going to lose accuracy at this high value. So one way and this is getting back to our quality essential ZZ that we can monitor that in how well they do is so different manufacturers choose different calibration curves but if you want them to be comparable and we want to know about their accuracy we can use a program and this is Rick. Wired under KLIA for laboratories doing high complexity testing they must do proficiency testing Sometimes this is known as external quality assessment so the intent here is to confirm the labs ability to purport accurate results OK So we want to know we have a target value and we want to send this out to thousands of laboratories have them report back to us in a way that blinded fashion they don't know what the results should be they cannot talk to each other they report back results centrally and then we can compare their results to see how accurate they are if a one laboratory is really off they then have to do remedial action to determine why they were off and why and how they can correct that. So clear requires that if you have those misses A.T.P. you have to do at least eighty percent in order to be successful and if you have eight less than eighty percent on repeated performances two out of three then the laboratory will have they could have increase sanctions that could it include closing the laboratory down or making them change the laboratory directors and the reason that they require them to change laboratory directors because this is an indication that overall quality is suffering in that laboratory and if they can't turn out a result that's accurate in these check samples these proficiency test and samples they aren't test they aren't turning out results on patients samples that are accurate either. So the way in which we measure how. Close these proficiency test Gene results are to each other is that we use a calculation of the coefficient of variation and this is calculated by the standard deviation so from the ME. In. Divided by the means so will take the mean of all those results and divide it divide the standard deviation by the mean and multiply it by hundred so you get a percentage so this is useful because it describes a variation within that group of data points such as getting from these different laboratories within a laboratory if you have a really good. High coefficient of variation it's going to tell you that you are able to consistently turn out to run the same results day after day so X. is always reported as EPS it's not X. minus one X. minus twenty seven X. plus one X. plus twenty seven it's it's X.. The interlock coefficient of variation this is what the proficiency testing organizations are to are monitoring they are telling us how accurate the results are they know what that should be and then by comparing all the results that they get by comparing them using the coefficient variation they can measure how accurate the test results are. It's also important to know that these interlock retore coefficient of variations are often segregated to different instruments so people who are using an instrument a are only compared to results generated by other users using instrument a they don't nest they will sometimes break out instrument a from instrument B. and calculate different coefficients of variation this is a practice that we see often with these home glucose monitors because the again the manufacturers have chosen different calibration curves so they are not necessarily over the full range getting accurate results but even though there in some cases some values here they're high or low are going. To be in accurate they're still valid valuable for monitoring at that target our reference range values. And consistently measuring over time so they're precise but they're not necessarily accurate when compared to other instruments and different instruments. So this is a a graph that just shows you this so this was sent out this graph just shows you a. Proficiency testing challenge that was sent out to a patient to various laboratories maybe these were even hospital wards that were doing the glucose tolerance testing and you can see that this is the target value fifty and this is the performance so by measuring the distance from this target we can determine the overall coefficient of variation. And for that the mean would be forty nine so the standard deviation is five point three and we see overall we have an eighty nine percent coefficient of variation If however we take these values and we break them down by method and only calculate the compare laboratories or. Results from method a method B. and method C. we're going to get different means different standard deviations and different coefficients of variation. And this example method A was a manufacturer that chose to capture the low values OK So there there are calibration line is going to to. Take into account those values so they did very well method B. is the laboratory method this is the standardized methods it was it was standardized over the import entire reportable right. Range and it's more cumbersome to report so if there coefficient of variation was ninety seven percent really high this method was a method that the manufacturer chose to. Take those values and put more emphasis on the high values so they're getting very low at the this low level of fifty they're getting a lower overall coefficient of variation and in fact they bring the whole group down. For all to eighty nine percent but individually we see that some methods have higher coefficients of variation. But now let's look how that what happens when you take that those same group and given the specimen at a high value and again the over all this is for hundreds the target value so overall the mean is for zero for the standard deviation is twenty nine and the C.V. is thirty ninety three percent but again let's break this down into those three separate methods the laboratory is still is at ninety six percent so it's very high so now we can conclude that method B. is both good at high values medium values and low values method A Now they're going to have. A lower than the average performance because again this was the set calibration her voice selected to capture those low values not the high values so they do suffer when you test them with high value specimens C. However now comes up and performs even better so the conclusion here is that these are good for high values and less accurate when testing low values. So why would a manufacturer do that why would they decide to do to focus on high values or low values Well they do that because there are interventions that occur at high value. Yes and other methods are going to have interventions that occur on low values so if it's fifty get some sugar in that person if it's forty you better get some add some extra insulin with in the next dosage so there are interventions that take place along that that that line of low values and high values and the manufacturers decide which one they're going to focus on. Another way to check on quality is to to look at quality control results so if you want to look on and approve these check samples perform per fish and sea testing are valuable for looking out the entire laboratories ability to turn out a result in general quality control is giving you information on a daily basis or run by run basis on how well at how accurate and how precise you are testing is occurring on each and every run or each and every day that specimens are tested. What you want in Cup quality control material is that you wanted to have a known value it needs to be stable because you want to use the same material on a monthly or even a quarterly or half year basis you want to be using the same lot if not the same vial because you want to have compare ability from day to day so it needs to be stable it should be as close of a matrix to the specimen as possible so if you're testing plasma or serum it should represent that it shouldn't be a pure aqueous solution of glucose it should have relevant computers that you're actually going to see in the specimen so this matrix effect is that we want to make sure we want to make sure that the matrix the underlying proteins carbohydrates cells are similar to ones that we're actually going to be testing in patients. It should call for the entire range of reportable results that means that you should have a low value a mid range value sometimes called the normal value and a high value OK So you want to test all three because you can you want to make sure that your calibration curve is working both low and high and you're not going to miss if you just target the mid range you may write not detect that you've lost linearity at the top at the high values or at the low values so you need to look at the entire reportable range. And your value shouldn't be lower than the values that you report are higher than values that you report but they should be within the range of reporting. So in summary. Laboratory data is essential and it's used on a. Chronic basis in chronic disease prevention programs and it's used for both methods that target primary secondary and tertiary prevention methods the methods in an alliance use for chronic disease prevention at any level should be vetted for accuracy and performance and ongoing quality assurance is needed and that includes point of care testing. There is much because these glucose monitors are used in wide variety of settings from hospital wards to gramma's who are blind and they're using them to and make life. Changing life saving or life threatening to citizens on a day to day basis on what they eat and how much insulin they inject they have to be reliable and so they need to be reliable and they need to be easily usable by this vast population in which they're there being used. So many laboratories that have the responsibility. Of actually overseeing a quality assurance pro. Ground for point of care test this would include doing quality control on a daily basis or weekly basis and it may also include doing check samples to find out if in fact those that instrument is performing in the at the same level that its peers out in the field are also being used. Thanks and have a great week.